敬钊毒素与电压门控钠钾通道相互作用的分子机制研究
|
摘要
蜘蛛毒液是含有不同的药理学特性的多肽分子的“富矿区”。多肽毒素具有高亲和力和多样化的药理学功能,因此,它们成为研究电压门控离子通道结构和功能关系的重要配体分子。Jingzhaotoxin-Ⅲ (JZTX-Ⅲ)是从有毒蜘蛛敬钊缨毛蛛毒液中分离出来的一种多肽神经毒素,由36个氨基酸残基组成。该毒素能特异性地抑制Nav1.5和KKv2.1通道激活,而对其它的大部分离子通道亚型无明显抑制作用。为了更好地阐明JZTX-Ⅲ与Kv2.1通道相互作用的分子机制,我们研究了JZTX-Ⅲ结合该通道的生物活性表面和结合受体位点。实验结果表明JZTX-Ⅲ能够捕获Kv2.1通道的电压敏感元件,抑制Kv2.1通道激活。丙氨酸替代电压敏感桨叶结构(S3b～S4)上的六个氨基酸残基Phe274、Lys280、 Ser281、Leu283、Gln284.和Va1288均大于7倍地降低了JZTX-Ⅲ的亲和力。其中,位于Kv2.1S3-S4胞外连接环上的Ser281是最关键的受体残基,该氨基酸残基被丙氨酸(Ala)、苯丙氨酸(Phe)、异亮氨酸(I1e)、缬氨酸(Val)和谷氨酸(Glu)替代后均能降低毒素的亲和力高于34倍。JZTX-Ⅲ结合Kv2.1通道的生物活性表面由四个疏水性残基(Trp8、Trp28、Trp30和Va133)以及三个电荷残基(Arg13、Lys15和Glu34)组成。虽然三个疏水性残基(Trp8、Trp28和Trp30)构成的疏水性斑片在JZTX-Ⅲ结合钠通道Nav1.5和钾通道Kv2.1的生物活性表面上重叠,但JZTX-Ⅲ抑制Nav1.5和Kv2.1这两种通道亚型的生物活性表面并不完全等同。三个氨基酸残基(Aspl、Glu3、Trp9)是JZTX-Ⅲ抑制Nav1.5通道的关键残基,而位于毒素另一面的三个电荷残基(Arg13、 Lvs15和Glu34)和一个疏水性残基Va133却关键性地影响了JZTX-Ⅲ结合Kv2.1通道。尽管这两个生物活性表面仅仅部分重叠,但是JZTX-Ⅲ能够通过捕获电压敏感元件的保守区域抑制这两种不同类型离子通道的激活。因此,我们的结果揭示了JZTX-Ⅲ采用特殊的分子机制抑制电压门控钠通道和电压门控钾通道。
为了更好地理解结构-功能关系,我们分析了JZTX-Ⅲ对表达在ND7/23细胞上的rNav1.8通道电流的影响。我们的研究结果显示JZTX-Ⅲ能够抑制rNav1.8通道的激活。根据hNav1.5和rNav1.8通道DIIS3～S4连接环的序列高度相似性,我们推测JZTX-Ⅲ能够作用于rNav1.8通道的位点4,作用机制类似于JZTX-Ⅲ捕获Nav1.5DIIS3～S4胞外连接环。因此,研究JZTX-Ⅲ与Nav1.8通道相互作用可能为揭示阻断Nav1.8通道的分子机制提供了前景。
Jingzhaotoxin-Ⅰ、-Ⅸ和-Ⅺ (JZTX-Ⅰ、-Ⅸ和-XI)是从有毒蜘蛛敬钊缨毛蛛毒液中分离得到的重要的神经毒素。它们含有三对二硫键,采用Ⅰ-Ⅳ、Ⅱ-V、Ⅲ-Ⅵ的配对方式,是典型的ICK结构模体的多肽分子。JZTX-Ⅰ由33个氨基酸残基组成,和目前报道的蜘蛛毒素的序列相似性均不高,仅与JZTX-ⅢI和GxTX1E有50%的序列同源性。JZTX-Ⅸ由35个氨基酸残基组成,但是该毒素与其它的蜘蛛毒素的序列相似性很高。例如,与HaTx1的相似性为63%,与HmTX-Ⅰ的相似性为63%,与SGTx1的相似性为60%,与JZTX-Ⅺ的相似性为71%。JZTX-Ⅰ、-Ⅸ和-Ⅺ是门控调节型毒素,它们能够加快Kv2.1通道的去激活动力学,使通道从激活状态往关闭状态转换,表明这些毒素可能通过电压敏感元件捕获的方式抑制通道的激活。这三种毒素抑制Kv2.1通道呈现明显的浓度依从性,抑制Kv2.1通道的IC50值分别为8.05、1.35和0.57μM。相对于JZTX-Ⅸ和JZTX-Ⅺ而言,JZTX-Ⅰ的氨基酸序列和表面结构明显不同,其结合Kv2.1通道的亲和力也非常低,抑制Kv2.1通道的IC50值分别是JZTX-Ⅸ和JZTX-Ⅺ的6倍和14倍。为了鉴定这些毒素结合Kv2.1通道的受体位点,从而进一步阐明毒素与通道相互作用之间的结构-功能关系,我们将Kv2.1通道S1-S2连接环和S3b-S4电压敏感浆叶结构上的单个氨基酸残基突变成丙氨酸,并采用双电极电压钳技术检测了JZTX-Ⅰ、 JZTX-Ⅸ和JZTX-Ⅺ与Kv2.1通道突变体的相互作用,鉴定了它们结合Kv2.1通道的受体位点。定点突变分析结果显示该通道S3b-S4电压敏感浆叶结构上的四个氨基酸残基(Ile273、Phe274、Glu277和Lys280)是决定JZTX-Ⅰ结合Kv2.1通道的关键受体残基,形成了JZTX-Ⅰ结合Kv2.1通道的受体位点。它们的丙氨酸突变体I273A、F274A、E277A和K280A分别降低了JZTX-Ⅰ的亲和力6倍、10倍、8倍和7倍。另外,位于S3b片段上的三个氨基酸残基(Ile273、Phe274和Glu277)也是决定JZTX-Ⅸ和JZTX-Ⅺ结合Kv2.1通道的关键残基,形成了这两个毒素的结合受体位点。这三个氨基酸残基被突变成丙氨酸后也大大地降低了JZTX-Ⅸ和JZTX-Ⅺ结合Kv2.1通道的亲和力。突变体I273A、F274A和E277A分别降低了JZTX-Ⅸ的敏感性9倍、19倍和16倍,降低了JZTX-Ⅺ的敏感性7倍、11倍和13倍。考虑到这些毒素都能够加快通道的去激活动力学,这些结果表明这三种蜘蛛毒素结合Kv2.1通道的受体位点部分重叠,均采用捕获静息状态电压敏感元件的方式抑制Kv2.1通道的激活。
JZTX-Ⅰ由33个氨基酸残基组成,其中6个半胱氨酸残基配对形成3对二硫键。前期工作推测JZTX-Ⅰ是一种类α-毒素,能够抑制大鼠心肌细胞上的TTX-R型钠通道、大鼠DRG神经元上TTX-S钠通道和棉铃虫幼虫神经元细胞钠通道的快速失活。采用全细胞膜片钳技术,我们进一步检测了JZTX-Ⅰ对钠通道亚型的影响,结果发现JZTX-Ⅰ能够高亲和力地结合钠通道亚型Nav1.5(IC50值为0.33μM). JZTX-Ⅰ抑制钠通道Nay1.5的快速失活具有时间依赖性和浓度依赖性,而且不影响该通道的激活和稳态失活动力学。丙氨酸扫描突变Nav1.5通道第四个同源区域DIV上的S3-S4胞外连接环发现突变体D1609是决定JZTX-Ⅰ捕获钠通道DIV的关键残基。这些结果表明JZTX-Ⅰ是位点3毒素,通过捕获钠通道DⅣ S3-S4胞外连接环延缓钠通道快速失活。
Spider venom is an important source of peptide molecules with different pharmacological properties. With high binding affinity and diverse pharmacological functions, peptide toxins are powerful ligands to investigate the structure-function relationships of voltage-gated ion channels. Jingzhaotoxin-Ⅲ (β-TRTX-Cj1α) is a36-residue peptide from the tarantula Chilobrachys jingzhao venom. The toxin is specific for Navl.5and Kv2.1channels over the majority of other ion channel subtypes. In order to better understand the molecular basis of JZTX-Ⅲ interaction with Kv2.1, we investigated the bioactive surface of JZTX-Ⅲ and the toxin binding site on Kv2.1. The results indicated that JZTX-Ⅲ docked onto the Kv2.1voltage sensor paddle. Alanine replacement of each residue Phe274, Lys280, Ser281, Leu283, Gln284, or Val288could decrease JZTX-Ⅲ affinity by>7-fold. Among them, Ser281is the most crucial determinant, and the substitution with Ala, Phe, lie, Val, or Glu increased the IC50value by>34-fold. The bioactive surface of JZTX-Ⅲ interacting with Kv2.1is composed of four hydrophobic residues (Trp8, Trp28, Trp30, and Val33) and three charged residues (Arg13, Lys15, and Glu34). Although a hydrophobic patch, mainly composed of Trp8, Trp28, and Trp30, was shared in the interaction with Nav1.5and Kv2.1, the bioactive surfaces of JZTX-Ⅲ interacting with both channels were not identical. Residues Asp1, Glu3, and Trp9were critical only for the inhibition of Nav1.5, whereas three charged residues (Arg13, Lys15, and Glu34) and one hydrophobic residue (Va133) were crucially involved in the interaction with Kv2.1. The bioactive surfaces of JZTX-Ⅲ interacting with Nav1.5and Kv2.1are only partially overlapping, but it inhibits these two distinct types of ion channels perhaps by recognizing a conserved binding motif on the voltage sensor paddle. Taken together, our study confirms special molecular mechanisms responsible for JZTX-Ⅲ binding to Nav and Kv channels.
To better understand the structure-function relationships, we analyzed the effects of JZTX-Ⅲ on rNav1.8currents expressed in ND7/23cells. Our finding showed that JZTX-Ⅲ could inhibit the activation of rNav1.8channel. Based on the high sequence similarity in the DIIS3-S4linkers of hNavl.5and rNavl.8, we propose that JZTX-Ⅲ inhibits rNavl.8channel perharps by binding to the receptor site4. JZTX-Ⅲ might be a peptide toxin with potential to shed light on the molecular mechanism of Nav1.8blocking.
Jingzhaotoxin-Ⅰ,-Ⅸ, and-Ⅺ (JZTX-Ⅰ,-Ⅸ, and-Ⅺ) are important neurotoxins from the tarantula Chilobrachys jingzhao venom. They have three disulfide bonds with the linkage of Ⅰ-Ⅳ, Ⅱ-Ⅴ, and Ⅲ-Ⅵ that is a typical pattern found in inhibitor cystine knot molecules. JZTX-Ⅰ is composed of33residues and exhibits limited sequence similarity with any reported peptide but nearly50%with JZTX-Ⅲ and GxTX1E. JZTX-Ⅸ has35amino acid residues and shares high sequence similarity with other peptides from the tarantula venoms such as HaTx1(63%), HmTX-Ⅰ (63%), SGTx1(60%), and JZTX-Ⅺ (71%). JZTX-Ⅰ,-Ⅸ, and-Ⅺ as gating modifiers are able to inhibit the activation of the potassium channel subtype Kv2.1and reduce currents through Kv2.1channels by modifying channel gating. They could significantly accelerate the kinetic of deactivation of Kv2.1channels, which reflects the transition from the activated state to the closed state, suggesting that these toxins might alter Kv2.1activation by docking onto the voltage sensor paddles. The inhibitions were concentration-dependent with the IC50values of8.05,1.35and0.57μM, respectively. In order to investigate their binding receptor sites on the Kv2.1channel, individual amino acid residue in the S1-S2linker and the S3b-S4paddle motif was mutated to alanine. Site-directed mutagenesis analysis demonstrated that four residues (Ile273, Phe274, Glu277, and Lys280) in the S3b-S4motif contributed to the formation of JZTX-I binding receptor site. The mutations I273A, F274A, E277A, and K280A reduced toxin binding affinity by6-,10-,8-, and7-fold, respectively. In addition, three residues (Ile273, Phe274, and Glu277) in the S3b region greatly reduced the binding affinity of both JZTX-Ⅸ and JZTX-Ⅸ for Kv2.1channel. The mutations I273A, F274A and E277A decreased JZTX-Ⅸ sensitivity by9-,19-,16-fold and JZTX-Ⅺ sensitivity by7-,11-,13-fold, respectively. Taken together with the findings that these toxins accelerate channel deactivation, these results suggest that they all inhibit Kv2.1activation by docking onto the voltage sensor paddles and trapping the voltage sensors in the closed state.
Our previous work have shown that JZTX-Ⅰ is an α-Like toxin that could inhibit channel fast inactivation kinetics of TTX-R sodium channels on rat cardiac myocytes and TTX-S sodium channels expressed on rat DRG neurons as well as cotton boll worm central nerve ganglian neurons. Using whole-cell patch-clamp technique, we analyzed the actions of JZTX-Ⅰ on voltage-gated sodium channel subtypes. Our findings indicated that JZTX-Ⅰ could inhibit Nav1.5channel with high affinity (IC50=0.33μM). The inhibition by JZTX-Ⅰ was in a time-dependent manner, and it had no effect on activation kinetics and steady-state inactivation. Alanine-scanning mutagenesis of Navl.5DIV S3-S4extracellular linker indicated that residue D1609was a critical molecular determinant for JZTX-Ⅰ binding. These results suggest that JZTX-Ⅰ is a site3toxin that inhibits channel inactivation by docking at the extracellular S3-S4linker of domain Ⅳ.
为了更好地理解结构-功能关系,我们分析了JZTX-Ⅲ对表达在ND7/23细胞上的rNav1.8通道电流的影响。我们的研究结果显示JZTX-Ⅲ能够抑制rNav1.8通道的激活。根据hNav1.5和rNav1.8通道DIIS3～S4连接环的序列高度相似性,我们推测JZTX-Ⅲ能够作用于rNav1.8通道的位点4,作用机制类似于JZTX-Ⅲ捕获Nav1.5DIIS3～S4胞外连接环。因此,研究JZTX-Ⅲ与Nav1.8通道相互作用可能为揭示阻断Nav1.8通道的分子机制提供了前景。
Jingzhaotoxin-Ⅰ、-Ⅸ和-Ⅺ (JZTX-Ⅰ、-Ⅸ和-XI)是从有毒蜘蛛敬钊缨毛蛛毒液中分离得到的重要的神经毒素。它们含有三对二硫键,采用Ⅰ-Ⅳ、Ⅱ-V、Ⅲ-Ⅵ的配对方式,是典型的ICK结构模体的多肽分子。JZTX-Ⅰ由33个氨基酸残基组成,和目前报道的蜘蛛毒素的序列相似性均不高,仅与JZTX-ⅢI和GxTX1E有50%的序列同源性。JZTX-Ⅸ由35个氨基酸残基组成,但是该毒素与其它的蜘蛛毒素的序列相似性很高。例如,与HaTx1的相似性为63%,与HmTX-Ⅰ的相似性为63%,与SGTx1的相似性为60%,与JZTX-Ⅺ的相似性为71%。JZTX-Ⅰ、-Ⅸ和-Ⅺ是门控调节型毒素,它们能够加快Kv2.1通道的去激活动力学,使通道从激活状态往关闭状态转换,表明这些毒素可能通过电压敏感元件捕获的方式抑制通道的激活。这三种毒素抑制Kv2.1通道呈现明显的浓度依从性,抑制Kv2.1通道的IC50值分别为8.05、1.35和0.57μM。相对于JZTX-Ⅸ和JZTX-Ⅺ而言,JZTX-Ⅰ的氨基酸序列和表面结构明显不同,其结合Kv2.1通道的亲和力也非常低,抑制Kv2.1通道的IC50值分别是JZTX-Ⅸ和JZTX-Ⅺ的6倍和14倍。为了鉴定这些毒素结合Kv2.1通道的受体位点,从而进一步阐明毒素与通道相互作用之间的结构-功能关系,我们将Kv2.1通道S1-S2连接环和S3b-S4电压敏感浆叶结构上的单个氨基酸残基突变成丙氨酸,并采用双电极电压钳技术检测了JZTX-Ⅰ、 JZTX-Ⅸ和JZTX-Ⅺ与Kv2.1通道突变体的相互作用,鉴定了它们结合Kv2.1通道的受体位点。定点突变分析结果显示该通道S3b-S4电压敏感浆叶结构上的四个氨基酸残基(Ile273、Phe274、Glu277和Lys280)是决定JZTX-Ⅰ结合Kv2.1通道的关键受体残基,形成了JZTX-Ⅰ结合Kv2.1通道的受体位点。它们的丙氨酸突变体I273A、F274A、E277A和K280A分别降低了JZTX-Ⅰ的亲和力6倍、10倍、8倍和7倍。另外,位于S3b片段上的三个氨基酸残基(Ile273、Phe274和Glu277)也是决定JZTX-Ⅸ和JZTX-Ⅺ结合Kv2.1通道的关键残基,形成了这两个毒素的结合受体位点。这三个氨基酸残基被突变成丙氨酸后也大大地降低了JZTX-Ⅸ和JZTX-Ⅺ结合Kv2.1通道的亲和力。突变体I273A、F274A和E277A分别降低了JZTX-Ⅸ的敏感性9倍、19倍和16倍,降低了JZTX-Ⅺ的敏感性7倍、11倍和13倍。考虑到这些毒素都能够加快通道的去激活动力学,这些结果表明这三种蜘蛛毒素结合Kv2.1通道的受体位点部分重叠,均采用捕获静息状态电压敏感元件的方式抑制Kv2.1通道的激活。
JZTX-Ⅰ由33个氨基酸残基组成,其中6个半胱氨酸残基配对形成3对二硫键。前期工作推测JZTX-Ⅰ是一种类α-毒素,能够抑制大鼠心肌细胞上的TTX-R型钠通道、大鼠DRG神经元上TTX-S钠通道和棉铃虫幼虫神经元细胞钠通道的快速失活。采用全细胞膜片钳技术,我们进一步检测了JZTX-Ⅰ对钠通道亚型的影响,结果发现JZTX-Ⅰ能够高亲和力地结合钠通道亚型Nav1.5(IC50值为0.33μM). JZTX-Ⅰ抑制钠通道Nay1.5的快速失活具有时间依赖性和浓度依赖性,而且不影响该通道的激活和稳态失活动力学。丙氨酸扫描突变Nav1.5通道第四个同源区域DIV上的S3-S4胞外连接环发现突变体D1609是决定JZTX-Ⅰ捕获钠通道DIV的关键残基。这些结果表明JZTX-Ⅰ是位点3毒素,通过捕获钠通道DⅣ S3-S4胞外连接环延缓钠通道快速失活。
Spider venom is an important source of peptide molecules with different pharmacological properties. With high binding affinity and diverse pharmacological functions, peptide toxins are powerful ligands to investigate the structure-function relationships of voltage-gated ion channels. Jingzhaotoxin-Ⅲ (β-TRTX-Cj1α) is a36-residue peptide from the tarantula Chilobrachys jingzhao venom. The toxin is specific for Navl.5and Kv2.1channels over the majority of other ion channel subtypes. In order to better understand the molecular basis of JZTX-Ⅲ interaction with Kv2.1, we investigated the bioactive surface of JZTX-Ⅲ and the toxin binding site on Kv2.1. The results indicated that JZTX-Ⅲ docked onto the Kv2.1voltage sensor paddle. Alanine replacement of each residue Phe274, Lys280, Ser281, Leu283, Gln284, or Val288could decrease JZTX-Ⅲ affinity by>7-fold. Among them, Ser281is the most crucial determinant, and the substitution with Ala, Phe, lie, Val, or Glu increased the IC50value by>34-fold. The bioactive surface of JZTX-Ⅲ interacting with Kv2.1is composed of four hydrophobic residues (Trp8, Trp28, Trp30, and Val33) and three charged residues (Arg13, Lys15, and Glu34). Although a hydrophobic patch, mainly composed of Trp8, Trp28, and Trp30, was shared in the interaction with Nav1.5and Kv2.1, the bioactive surfaces of JZTX-Ⅲ interacting with both channels were not identical. Residues Asp1, Glu3, and Trp9were critical only for the inhibition of Nav1.5, whereas three charged residues (Arg13, Lys15, and Glu34) and one hydrophobic residue (Va133) were crucially involved in the interaction with Kv2.1. The bioactive surfaces of JZTX-Ⅲ interacting with Nav1.5and Kv2.1are only partially overlapping, but it inhibits these two distinct types of ion channels perhaps by recognizing a conserved binding motif on the voltage sensor paddle. Taken together, our study confirms special molecular mechanisms responsible for JZTX-Ⅲ binding to Nav and Kv channels.
To better understand the structure-function relationships, we analyzed the effects of JZTX-Ⅲ on rNav1.8currents expressed in ND7/23cells. Our finding showed that JZTX-Ⅲ could inhibit the activation of rNav1.8channel. Based on the high sequence similarity in the DIIS3-S4linkers of hNavl.5and rNavl.8, we propose that JZTX-Ⅲ inhibits rNavl.8channel perharps by binding to the receptor site4. JZTX-Ⅲ might be a peptide toxin with potential to shed light on the molecular mechanism of Nav1.8blocking.
Jingzhaotoxin-Ⅰ,-Ⅸ, and-Ⅺ (JZTX-Ⅰ,-Ⅸ, and-Ⅺ) are important neurotoxins from the tarantula Chilobrachys jingzhao venom. They have three disulfide bonds with the linkage of Ⅰ-Ⅳ, Ⅱ-Ⅴ, and Ⅲ-Ⅵ that is a typical pattern found in inhibitor cystine knot molecules. JZTX-Ⅰ is composed of33residues and exhibits limited sequence similarity with any reported peptide but nearly50%with JZTX-Ⅲ and GxTX1E. JZTX-Ⅸ has35amino acid residues and shares high sequence similarity with other peptides from the tarantula venoms such as HaTx1(63%), HmTX-Ⅰ (63%), SGTx1(60%), and JZTX-Ⅺ (71%). JZTX-Ⅰ,-Ⅸ, and-Ⅺ as gating modifiers are able to inhibit the activation of the potassium channel subtype Kv2.1and reduce currents through Kv2.1channels by modifying channel gating. They could significantly accelerate the kinetic of deactivation of Kv2.1channels, which reflects the transition from the activated state to the closed state, suggesting that these toxins might alter Kv2.1activation by docking onto the voltage sensor paddles. The inhibitions were concentration-dependent with the IC50values of8.05,1.35and0.57μM, respectively. In order to investigate their binding receptor sites on the Kv2.1channel, individual amino acid residue in the S1-S2linker and the S3b-S4paddle motif was mutated to alanine. Site-directed mutagenesis analysis demonstrated that four residues (Ile273, Phe274, Glu277, and Lys280) in the S3b-S4motif contributed to the formation of JZTX-I binding receptor site. The mutations I273A, F274A, E277A, and K280A reduced toxin binding affinity by6-,10-,8-, and7-fold, respectively. In addition, three residues (Ile273, Phe274, and Glu277) in the S3b region greatly reduced the binding affinity of both JZTX-Ⅸ and JZTX-Ⅸ for Kv2.1channel. The mutations I273A, F274A and E277A decreased JZTX-Ⅸ sensitivity by9-,19-,16-fold and JZTX-Ⅺ sensitivity by7-,11-,13-fold, respectively. Taken together with the findings that these toxins accelerate channel deactivation, these results suggest that they all inhibit Kv2.1activation by docking onto the voltage sensor paddles and trapping the voltage sensors in the closed state.
Our previous work have shown that JZTX-Ⅰ is an α-Like toxin that could inhibit channel fast inactivation kinetics of TTX-R sodium channels on rat cardiac myocytes and TTX-S sodium channels expressed on rat DRG neurons as well as cotton boll worm central nerve ganglian neurons. Using whole-cell patch-clamp technique, we analyzed the actions of JZTX-Ⅰ on voltage-gated sodium channel subtypes. Our findings indicated that JZTX-Ⅰ could inhibit Nav1.5channel with high affinity (IC50=0.33μM). The inhibition by JZTX-Ⅰ was in a time-dependent manner, and it had no effect on activation kinetics and steady-state inactivation. Alanine-scanning mutagenesis of Navl.5DIV S3-S4extracellular linker indicated that residue D1609was a critical molecular determinant for JZTX-Ⅰ binding. These results suggest that JZTX-Ⅰ is a site3toxin that inhibits channel inactivation by docking at the extracellular S3-S4linker of domain Ⅳ.
引文
[1]Liang, S.P. Proteome and peptidome profiling of spider venoms[J]. Expert Rev Proteomics,2008, (5):731-746.
[2]Rash, L.D. & W.C. Hodgson. Pharmacology and biochemistry of spider venoms[J]. Toxicon,2002,(40):225-254.
[3]Estrada, G., Villegas, E., Corzo, G. Spider venoms:a rich source of acylpolyamines and peptides as new leads for CNS drugs[J]. Nat Prod Rep, 2007,(24):145-161.
[4]Klint, J.K., Senff, S., Rupasinghe, D.B., Er, S.Y., Herzig, V., Nicholson, G.M., King, G.F. Spider-venom peptides that target voltage-gated sodium channels: Pharmacological tools and potential therapeutic leads[J]. Toxicon,2012, (60): 478-491.
[5]Sollod, B.L., Wilson, D., Zhaxybayeva, O., Gogarten, J.P., Drinkwater, R., King, GF. Were arachnids the first to use combinatorial peptide libraries? [J]. Peptides,2005, (26):131-139.
[6]Colgrave, M.L. & D.J. Craik.Thermal, Chemical, and Enzymatic Stability of the Cyclotide Kalata B1:□ The Importance of the Cyclic Cystine Knot[J]. Biochemistry,2004, (43):5965-5975.
[7]Chen, J.-Q., Zhang, Y.-Q., Dai, J., Luo, Z.-M., Liang, S.-P. Antinociceptive effects of intrathecally administered huwentoxin-I, a selective N-type calcium channel blocker, in the formalin test in conscious rats[J]. Toxicon, 2005,(45):15-20.
[8]Pinheiro, A.C.N., Gomez, R.S., Massensini, A.R., Cordeiro, M.N., Richardson, M., Romano-Silva, M.A., Prado, M.A.M., Marco, L.D., Gomez, M.V. Neuroprotective effect on brain injury by neurotoxins from the spider Phoneutria nigriventer[J]. Neurochem. Int,2006, (49):543-547.
[9]Isom, L., De Jongh, K., Patton, D., Reber, B., Offord, J., Charbonneau, H., Walsh, K., Goldin, A., Catterall, W. Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel [J]. Science,1992, (256):839-842.
[10]Isom, L.L., Ragsdale, D.S., De Jongh, K.S., Westenbroek, R.E., Reber, B.F.X., Scheuer, T., Catterall, W.A. Structure and function of the 22 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif[J]. Cell,1995, (83):433-442.
[11]Morgan, K., Stevens, E.B., Shah, B., Cox, P.J., Dixon, A.K., Lee, K., Pinnock, J. R.D., P.J. Hughes, K. Richardson, Jackson, A.P. β3:An additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics[J]. Proc. Natl. Acad. Sci. U.S.A,2000, (97): 2308-2313.
[12]Spampanato, J., Escayg, A., Meisler, M.H., Goldin, A.L. Generalized epilepsy with febrile seizures plus type 2 mutation W1204R alters voltage-dependent gating of Nav1.1 sodium channels[J]. Neuroscience,2003, (116):37-48.
[13]Chraibi, A., Schnizler, M., Clauss, W., Horisberger, J.D. Effects of 8-cpt-cAMP on the Epithelial Sodium Channel Expressed in Oocytes[J]. J. Membr. Biol, 2001,(183):15-23.
[14]Catterall, W. Structure and function of voltage-sensitive ion channels[J]. Science, 1988, (242):50-61.
[15]Saez, N.J., Senff, S., Jensen, J.E., Er, S.Y., Herzig, V., Rash, L.D., King, G.F. Spider-Venom Peptides as Therapeutics [J]. Toxins,2010, (2):2851-2871.
[16]Fletcher, J.I., Smith, R., Odonoghue, S.I., Nilges, M., Connor, M., Howden, M.J. Christie, M.E.H., King, G.F. The structure of a novel insecticidal neurotoxin, omega-atracotoxin-HV1, from the venom of an Australian funnel web spider[J]. Nat. Struct. Biol,1997, (5):59-66.
[17]Payandeh, J., Scheuer, T., Zheng, N., Catterall, W.A. The crystal structure of a voltage-gated sodium channel[J]. Nature,2011, (475):353-358.
[18]Yang, N., George, A.L., Horn, R. Molecular Basis of Charge Movement in Voltage-Gated Sodium Channels[J]. Neuron,1996, (16):113-122.
[19]Goldin, A.L. Mechanisms of sodium channel inactivation[J]. Cur Opinion in Neurobiology,2003, (13):284-290.
[20]Cestele, S., Scheuer, T., Mantegazza, M., Rochat, H., Catterall, W.A. Neutralization of Gating Charges in Domain Ⅱ of the Sodium Channel a Subunit Enhances Voltage-Sensor Trapping by a β-Scorpion Toxin[J]. J. Gen. Physiol,2001, (118):291-302.
[21]Catterall, W.A. From Ionic Currents to Molecular Mechanisms:The Structure and Function of Voltage-Gated Sodium Channels[J]. Neuron,2000, (26): 13-25.
[22]Penzotti, J.L., Fozzard, H.A., Lipkind, G.M., Dudley Jr, S.C. Differences in Saxitoxin and Tetrodotoxin Binding Revealed by Mutagenesis of the Na+ Channel Outer Vestibule[J]. Biophys J.1998, (75):2647-2657.
[23]Catterall, W.A. Structure and function of voltage-gated ion channels[J]. Trends Neurosci,1993, (16):500-506.
[24]Cestele, S., Catterall, W.A. Molecular mechanisms of neurotoxin action on voltage-gated sodium channels[J]. Biochimie,2000, (82):883-892.
[25]Isom, L.L. Sodium Channel β Subunits:Anything but Auxiliary[J]. Neuroscientist,2001, (7):42-54.
[26]Yu, F.H., Westenbroek, R.E., Silos-Santiago, I., McCormick, K.A., Lawson, D., Ge, P., Ferriera, H., Lilly, J., DiStefano, P.S., Catterall, W.A., Scheuer, T., Curtis, R. Sodium Channel β4, a New Disulfide-Linked Auxiliary Subunit with Similarity to β2[J]. J. Neurosci,2003, (23):7577-7585.
[27]Whitaker, W.R.J., Clare, J.J., Powell, A.J., Chen, Y.H., Faull, R.L.M., Emson, P.C. Distribution of voltage-gated sodium channel α-subunit and β-subunit mRNAs in human hippocampal formation, cortex, and cerebellum[J]. J. Comp. Neurol,2000, (422):123-139.
[28]Meadows, L., Malhotra, J.D., Stetzer, A., Isom, L.L., Ragsdale, D.S. The intracellular segment of the sodium channel β1 subunit is required for its efficient association with the channel a subunit[J]. J Neurochem,2001, (76): 1871-1878.
[29]Oh, Y., Sashihara, S., Black, J.A., Waxman, S.G. Na+ channel β1 subunit mRNA: differential expression in rat spinal sensory neurons[J]. Brain Res. Mol. Brain Res,1995, (30):357-361.
[30]Shah, B.S., Stevens, E.B., Gonzalez, M.I., Bramwell, S., Pinnock, R.D., Lee, K. Dixon, A.K. β3, a novel auxiliary subunit for the voltage-gated sodium channel, is expressed preferentially in sensory neurons and is upregulated in the chronic constriction injury model of neuropathic pain[J]. Eur J Neurosci, 2000, (12):3985-3990.
[31]Auld, V.J., Goldin, A.L., Krafte, D.S., Catterall, W.A., Lester, H.A., Davidson, N., Dunn, R.J. A neutral amino acid change in segment IIS4 dramatically alters the gating properties of the voltage-dependent sodium channel [J]. Proc. Nad. Acad. Sci. U.S.A,1990, (87):323-327.
[32]Rohl, C.A., Boeckman, F.A., Baker, C., Scheuer, T., Catterall, W.A., Klevit, R.E. Solution Structure of the Sodium Channel Inactivation Gate[J]. Biochemistry.1998, (38):855-861.
[33]Miyamoto, K., Nakagawa, T., Kuroda, Y., Kanaori, K. Solution structures of the inactivation gate particle peptides of rat brain type-IIA and human heart sodium channels in SDS micelles[J]. J. Pept. Res,2001, (57):203-214.
[34]Catterall, W.A., Goldin, A.L., Waxman, S.G. International Union of Pharmacology. XLVII. Nomenclature and Structure-Function Relationships of Voltage-Gated Sodium Channels[J]. Pharmacol. Rev,2005, (57):397-409.
[35]Catterall, W.A., Perez-Reyes, E., Snutch, T.P., Striessnig, J. International Union of Pharmacology. XLVIII. Nomenclature and Structure-Function Relationships of Voltage-Gated Calcium Channels[J]. Pharmacol. Rev,2005, (57):411-425.
[36]Ogata, N., Tatebayashi, H. Kinetic analysis of two types of Na+ channels in rat dorsal root ganglia[J]. J. Physio,1993, (466):9-37.
[37]Herzog, R.I., Liu, C., Waxman, S.G., Cummins, T.R. Calmodulin Binds to the C Terminus of Sodium Channels Nav1.4 and Navl.6 and Differentially Modulates Their Functional Properties[J]. J. Neurosci,2003, (23): 8261-8270.
[38]Maier, S.K.G., Westenbroek, R.E., Yamanushi, T.T., Dobrzynski, H., Boyett, M.R., Catterall, W.A., Scheuer, T. An unexpected requirement for brain-type sodium channels for control of heart rate in the mouse sinoatrial node[J]. Proc. Natl. Acad. Sci. U.S.A,2003, (100):3507-3512.
[39]Oda, A., Ohashi, H., Komori, S., Iida, H., Dohi, S. Characteristics of Ropivacaine Block of Na+ Channels in Rat Dorsal Root Ganglion Neurons[J]. Anesth. Analg,2000, (91):1213-1220.
[40]Lopreato, G.F., Lu, Y, Southwell, A., Atkinson, N.S., Hillis, D.M., Wilcox, T.P., Zakon, H.H. Evolution and divergence of sodium channel genes in vertebrates [J]. Proc. Natl. Acad. Sci. U.S.A,2001, (98):7588-7592.
[41]Goldin, A.L., Barchi, R.L., Caldwell, J.H., Hofmann, F., Howe, J.R., Hunter, J.C., Kallen, R.G., Mandel, G., Meisler, M.H., Netter, Y.B., Noda, M., Tamkun, M.M., Waxman, S.G., Wood, J.N. Catterall, W.A. Nomenclature of Voltage-Gated Sodium Channels[J]. Neuron,2000, (28): 365-368.
[42]Dib-Hajj, S.D., Black, J.A., Waxman, S.G. Voltage-Gated Sodium Channels: Therapeutic Targets for Pain[J]. Pain Medicine,2009, (10):1260-1269.
[43]Hains, B.C., Klein, J.P., Saab, C.Y., Craner, M.J., Black, J.A., Waxman, S.G. Upregulation of Sodium Channel Navl.3 and Functional Involvement in Neuronal Hyperexcitability Associated with Central Neuropathic Pain after Spinal Cord Injury[J]. J. Neurosci,2003, (23):8881-8892.
[44]Cummins, T.R., Dib-Hajj, S.D., Waxman, S.G. Electrophysiological Properties of Mutant Navl.7 Sodium Channels in a Painful Inherited Neuropathy[J]. J. Neurosci,2004, (24):8232-8236.
[45]Laird, J.M.A., Souslova, V, Wood, J.N., Cervero, F. Deficits in Visceral Pain and Referred Hyperalgesia in Navl.8 (SNS/PN3)-Null Mice[J]. J. Neurosci, 2002, (22):8352-8356.
[46]Escoubas, P., Diochot, S., Corzo, G. Structure and pharmacology of spider venom neurotoxins[J]. Biochimie,2000, (82):893-907.
[47]Smith, J.J., Blumenthal, K.M. Site-3 sea anemone toxins:Molecular probes of gating mechanisms in voltage-dependent sodium channels[J]. Toxicon,2007, (49):159-170.
[48]Hanck, D.A., Sheets, M.F. Site-3 toxins and cardiac sodium channels[J]. Toxicon,2007,(49):181-193.
[49]Nicholson, G.M., Walsh, R., Little, M.J., Tyler, M.I. Characterisation of the effects of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus on sodium channel activation and inactivation[J]. Eur. J. Physiol,1998,(436):117-126.
[50]Szeto, T.H., Birinyi-Strachan, L.C., Smith, R., Connor, M., Christie, M.J., King, G.F., Nicholson, G.M. Isolation and pharmacological characterisation of δ-atracotoxin-Hv1b, a vertebrate-selective sodium channel toxin[J]. FEBS Letters,2000, (470):293-299.
[51]Bosmans, F., Tytgat, J. Voltage-gated sodium channel modulation by scorpion α-toxins[J]. Toxicon,2007, (49):142-158.
[52]Goudet, C., Chi, C.-W., Tytgat, J. An overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch[J]. Toxicon,2002, (40): 1239-1258.
[53]Little, M.J., Wilson, H., Zappia, C., Cestele, S., Tyler, M.I., Martin-Eauclaire, M.-F., Gordon, D., Nicholson, G.M.δ-Atracotoxins from Australian funnel-web spiders compete with scorpion a-toxin binding on both rat brain and insect sodium channels[J]. FEBS Letters,1998, (439):246-252.
[54]Pallaghy, P.K., Norton, R.S., Nielsen, K.J., Craik, D.J. A common structural motif incorporating a cystine knot and a triple-stranded β-sheet in toxic and inhibitory polypeptides[J].Protein Sci,1994,(3):1833-1839.
[55]Corzo, G., Escoubas, P., Stankiewicz, M., Pelhate, M., Kristensen, C.P., Nakajima, T. Isolation, synthesis and pharmacological characterization of δ-palutoxins IT, novel insecticidal toxins from the spider Paracoelotes luctuosus (Amaurobiidae) [J]. Eur JBiochem,2000, (267):5783-5795.
[56]Skinner, W.S., Adams, M.E., Quistad, G.B., Kataoka, H., Cesarin, B.J., Enderlin, F.E., Schooley, D.A. Purification and characterization of two classes of neurotoxins from the funnel web spider, Agelenopsis aperta[J]. J Biol Chem, 1989, (264):2150-2155.
[57]Stapleton, A., Blankenship, D.T., Ackermann, B.L., Chen, T.M., Gorder, G.W., Manley, G.D., Palfreyman, M.G., Coutant, J.E., Cardin, A.D. Curtatoxins. Neurotoxic insecticidal polypeptides isolated from the funnel-web spider Hololena curta[J]. J Biol Chem,1990, (265):2054-2059.
[58]Matavel, A., Cruz, J.S., Penaforte, C.L., Araujo, D.A.M., Kalapothakis, E., Prado, V.F., Diniz, C.R., Cordeiro, M.N., Beirao, P.S.L. Electrophysiological characterization and molecular identification of the Phoneutria nigriventer peptide toxin PnTx2-6[J]. FEBS Letters,2002, (523):219-223.
[59]Sheumack, D.D., Claassens, R., Whiteley, N.M., Howden, M.H.H. Complete amino acid sequence of a new type of lethal neurotoxin from the venom of the funnel-web spider Atrax robustus[J]. FEBS Letters,1985, (181):154-156.
[60]Little, M.J., Zappia, C., Gilles, N., Connor, M., Tyler, M.I., Martin-Eauclaire, M.-F., Gordon, D., Nicholson, G.M.8-Atracotoxins from Australian Funnel-web Spiders Compete with Scorpion α-Toxin Binding but Differentially Modulate Alkaloid Toxin Activation of Voltage-gated Sodium Channels[J]. J Biol Chem,1998, (273):27076-27083.
[61]Calegario Oliveira, L., De Lima, M.E., Pimenta, A.M.C., Mansuelle, P., Rochat, H., Cordeiro, M.N., Richardson, M., Figueiredo, S.G. PnTx4-3, a new insect toxin from Phoneutria nigriventer venom elicits the glutamate uptake inhibition exhibited by PhTx4 toxic fraction[J]. Toxicon,2003, (42):793-800.
[62]Wang, M., Liu, Q., Luo, H., Li, J., Tang, J., Xiao, Y, Liang, S. Jingzhaotoxin-Ⅱ, a novel tarantula toxin preferentially targets rat cardiac sodium channel [J]. Biochem Pharmacol,2008, (76):1716-1727.
[63]Cestele, S., Qu, Y., Rogers, J.C., Rochat, H., Scheuer, T., Catterall, W.A. Voltage Sensor Trapping:Enhanced Activation of Sodium Channels by 2-Scorpion Toxin Bound to the S3 S4 Loop in Domain II[J]. Neuron,1998, (21):919-931.
[64]Cestele, S., Yarov-Yarovoy, V., Qu, Y, Sampieri, F., Scheuer, T., Catterall, W.A. Structure and Function of the Voltage Sensor of Sodium Channels Probed by a β-Scorpion Toxin[J]. J Biol Chem,2006, (281):21332-21344.
[65]Middleton, R.E., Warren, V.A., Kraus, R.L., Hwang, J.C., Liu, C.J., Dai, G., Brochu, R.M., Kohler, M.G., Gao, Y.-D., Garsky, V.M., Bogusky, M.J., Mehl, J.T., Cohen, C.J., Smith, M.M. Two Tarantula Peptides Inhibit Activation of Multiple Sodium Channels[J]. Biochemistry,2002, (41):14734-14747.
[66]Priest, B.T., Blumenthal, K.M., Smith, J.J., Warren, V.A., Smith, M.M. ProTx-Ⅰ and ProTx-Ⅱ:Gating modifiers of voltage-gated sodium channels[J]. Toxicon, (49):194-201.
[67]Xiao, Y, Luo, X., Kuang, F., Deng, M., Wang, M., Zeng, X., Liang, S. Synthesis and characterization of huwentoxin-IV, a neurotoxin inhibiting central neuronal sodium channels[J]. Toxicon,2008, (51):230-239.
[68]Wolfner, M.F., Harada, H.A., Bertram, M.J., Stelick, T.J., Kraus, K.W., Kalb, J.M., Lung, Y.O., Neubaum, D.M., Park, M., Tram, U. New Genes for Male Accessory Gland Proteins in Drosophila melanogaster[J]. Insect Biochem. Mol. Biol,1997, (27):825-834.
[69]Corzo, G., Sabo, J.K., Bosmans, F., Billen, B., Villegas, E., Tytgat, J., Norton, R.S. Solution Structure and Alanine Scan of a Spider Toxin That Affects the Activation of Mammalian Voltage-gated Sodium Channels[J]. J Biol Chem, 2007, (282):4643-4652.
[70]Xiao, Y, Tang, J., Yang, Y, Wang, M., Hu, W., Xie, J., Zeng, X., Liang, S. Jingzhaotoxin-Ⅲ, a Novel Spider Toxin Inhibiting Activation of Voltage-gated Sodium Channel in Rat Cardiac Myocytes[J]. J. Biol. Chem, 2004, (279):26220-26226.
[71]Corzo, G., Gilles, N., Satake, H., Villegas, E., Dai, L., Nakajima, T., Haupt, J. Distinct primary structures of the major peptide toxins from the venom of the spider Macrothele gigas that bind to sites 3 and 4 in the sodium channel[J]. FEBS Letters,2003, (547):43-50.
[72]Peng, K., Shu, Q., Liu, Z., Liang, S. Function and Solution Structure of Huwentoxin-Ⅳ, a Potent Neuronal Tetrodotoxin (TTX)-sensitive Sodium Channel Antagonist from Chinese Bird Spider Selenocosmia huwena[J]. J. Biol. Chem,2002, (277):47564-47571.
[73]Coetzee, W.A., Amarillo, Y., Chiu, J., Chow, A., Lau, D., McCormack, T.O.M., Morena, H., Nadal, M.S., Ozaita, A., Pountney, D., Saganich, M., De Miera, E.V.-S., Rudy, B. Molecular Diversity of K+ Channels [J]. Ann. Ny Acad. Sci,1999,(868):233-255.
[74]Lu, Z., Klem, A.M., Ramu, Y. Ion conduction pore is conserved among potassium channels[J]. Nature,2001, (413):809-813.
[75]Jiang, Y., Lee, A., Chen, J., Ruta, V., Cadene, M., Chait, B.T., MacKinnon, R. X-ray structure of a voltage-dependent K+ channel[J]. Nature,2003, (423): 33-41.
[76]Long, S.B., Tao, X., Campbell, E.B., MacKinnon, R. Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment[J]. Nature,2007, (450):376-382.
[77]Corzo, G., Papp, F., Varga, Z., Barraza, O., Espino-Solis, P.G., Rodriguez de la Vega, R.C., Gaspar, R., Panyi, G., Possani, L.D. A selective blocker of Kvl.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus[J]. Biochem Pharmacol,2008, (76):1142-1154.
[78]Ruta, V., Jiang, Y., Lee, A., Chen, J., MacKinnon, R. Functional analysis of an archaebacterial voltage-dependent K+ channel[J]. Nature,2003, (422): 180-185.
[79]Miller, C. See potassium run[J]. Nature,2001, (414):23-24.
[80]Doyle, D.A., Cabral, J.M., Pfuetzner, R.A., Kuo, A., Gulbis, J.M., Cohen, S.L Chait, B.T., MacKinnon, R. The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity[J]. Science,1998, (280): 69-77.
[81]Long, S.B., Campbell, E.B., MacKinnon, R. Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel[J]. Science,2005, (309): 897-903.
[82]Shieh, C.-C., Coghlan, M., Sullivan, J.P., Gopalakrishnan, M. Potassium Channels:Molecular Defects, Diseases, and Therapeutic Opportunities [J]. Pharmacol. Rev,2000, (52):557-594.
[83]Schweitz, H., Bruhn, T., Guillemare, E., Moinier, D., Lancelin, J.-M., Beress, L., Lazdunski, M., Kalicludines and Kaliseptine[J]. J Biol Chem,1995, (270): 25121-25126.
[84]Escoubas, P., Diochot, S., Celerier, M.-L., Nakajima, T., Lazdunski, M. Novel Tarantula Toxins for Subtypes of Voltage-Dependent Potassium Channels in the Kv2 and Kv4 Subfamilies[J]. Mol. Pharmacol.2002, (62):48-57.
[85]Wang, F.C., Bell, N., Reid, P., Smith, L.A., McIntosh, P., Robertson, B., Dolly, J.O. Identification of residues in dendrotoxin K responsible for its discrimination between neuronal K+ channels containing Kv1.1 and 1.2 a subunits[J]. Eur J Bioche,1999, (263):222-229.
[86]Lee, C.W., Kim, S., Roh, S.H., Endoh, H., Kodera, Y, Maeda, T., Kohno, T., Wang, J.M., Swartz, K.J., Kim, J.I. Solution Structure and Functional Characterization of SGTx1, a Modifier of Kv2.1 Channel Gating[J]. Biochemistry,2004, (43):890-897.
[87]Takahashi, H., Kim, J.I., Min, H.J., Sato, K., Swartz, K.J., Shimada, I. Solution structure of hanatoxin1, a gating modifier of voltage-dependent K+ channels: common surface features of gating modifier toxins[J]. J. Mol. Biol,2000, (297):771-780.
[88]Oswald, R.E., Suchyna, T.M., McFeeters, R., Gottlieb, P., Sachs, F. Solution Structure of Peptide Toxins That Block Mechanosensitive Ion Channels[J]. J Biol Chem,2002, (277):34443-34450.
[89]Swartz, K.J., MacKinnon, R. An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula[J]. Neuron,1995, (15): 941-949.
[90]Lee, H.C., Wang, J.M., Swartz, K.J. Interaction between Extracellular Hanatoxin and the Resting Conformation of the Voltage-Sensor Paddle in Kv Channels[J]. Neuron,2003, (40):527-536.
[91]Swartz, K.J. & R. MacKinnon. Mapping the Receptor Site for Hanatoxin, a Gating Modifier of Voltage-Dependent K+ Channels[J]. Neuron,1997, (18): 675-682.
[92]Li-Smerin, Y. & K.J. Swartz. Localization and Molecular Determinants of the Hanatoxin Receptors on the Voltage-Sensing Domains of a K+ Channel[J]. J. Gen. Physiol,2000, (115):673-684.
[93]Revell Phillips, L., Milescu, M., Li-Smerin, Y., Mindell, J.A., Kim, J.I., Swartz, K.J. Voltage-sensor activation with a tarantula toxin as cargo[J]. Nature,2005, (436):857-860.
[94]Marvin, L., De, E., Cosette, P., Gagnon, J., Molle, G., Lange, C. Isolation, amino acid sequence and functional assays of SGTx1[J]. Eur J Biochem, 1999, (265):572-579.
[95]Wang, J.M., Roh, S.H., Kim, S., Lee, C.W., Kim, J.I., Swartz, K.J. Molecular Surface of Tarantula Toxins Interacting with Voltage Sensors in Kv Channels[J].J. Gen. Physiol,2004, (123):455-467.
[96]Zarayskiy, V.V., Balasubramanian, G, Bondarenko, V.E., Morales, M.J. Heteropoda toxin 2 is a gating modifier toxin specific for voltage-gated K+ channels of the Kv4 family[J]. Toxicon,2005, (45):431-442.
[97]DeSimone, C.V., Zarayskiy, V.V., Bondarenko, V.E., Morales, M.J. Heteropoda Toxin 2 Interaction with Kv4.3 and Kv4.1 Reveals Differences in Gating Modification[J]. Mol. Pharmacol,2011, (80):345-355.
[98]DeSimone, C.V., Lu, Y., Bondarenko, V.E., Morales, M.J. S3b Amino Acid Substitutions and Ancillary Subunits Alter the Affinity of Heteropoda venatoria Toxin 2 for Kv4.3[J]. Mol. Pharmacol,2009, (76):125-133.
[99]Sanguinetti, M.C., Johnson, J.H., Hammerland, L.G., Kelbaugh, P.R., Volkmann, R.A., Saccomano, N.A., Mueller, A.L. Heteropodatoxins:Peptides Isolated from Spider Venom that Block Kv4.2 Potassium Channels[J]. Mol. Pharmacol,1997, (51):491-498.
[100]Lee, S.-Y. & R. MacKinnon, A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom[J]. Nature,2004. (430):232-235.
[101]Liao, Z., Yuan, C. Deng, M., Li, J., Chen, J., Yang, Y., Hu, W., Liang, S. Solution Structure and Functional Characterization of Jingzhaotoxin-Ⅺ:□ A Novel Gating Modifier of both Potassium and Sodium Channels[J]. Biochemistry,2006, (45):15591-15600.
[102]Yuan, C., Liao, Z., Zeng, X., Dai, L., Kuang, F., Liang, S. Jingzhaotoxin-XII, a gating modifier specific for Kv4.1 channels[J]. Toxicon,2007, (50):646-652.
[103]Zeng, X., Deng, M., Lin, Y, Yuan, C., Pi, J., Liang, S. Isolation and characterization of Jingzhaotoxin-V, a novel neurotoxin from the venom of the spider Chilobrachys jingzhao[J]. Toxicon,2007, (49):388-399.
[104]Jung, H.J., Lee, J.Y, Kim, S.H., Eu, Y.-J., Shin, S.Y, Milescu, M., Swartz, K.J., Kim, J.I. Solution Structure and Lipid Membrane Partitioning of VSTx1, an Inhibitor of the KvAP Potassium Channel[J]. Biochemistry,2005, (44): 6015-6023.
[105]Yuan, C., Jin, Q., Tang, X., Hu, W., Cao, R., Yang, S., Xiong, J., Xie, C., Xie, J., Liang, S. Proteomic and Peptidomic Characterization of the Venom from the Chinese Bird Spider, Ornithoctonus huwena Wang[J]. J. Proteome Res, 2007, (6):2792-2801.
[106]Tang, X., Zhang, Y, Hu, W., Xu, D., Tao, H., Yang, X., Li, Y, Jiang, L., Liang, S. Molecular Diversification of Peptide Toxins from the Tarantula Haplopelma hainanum (Ornithoctonus hainana) Venom Based on Transcriptomic, Peptidomic, and Genomic Analyses[J]. J. Proteome Res, 2010, (9):2550-2564.
[107]Liao, Z., Cao, J., Li, S., Yan, X., Hu, W., He, Q., Chen, J., Tang, J., Xie, J., Liang, S. Proteomic and peptidomic analysis of the venom from Chinese tarantula Chilobrachys jingzhao[J]. Proteomics,2007, (7):1892-1907.
[108]Suchyna, T.M., Tape, S.E., Koeppe, R.E., Andersen, O.S., Sachs, F., Gottlieb, P.A. Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers[J]. Nature,2004, (430):235-240.
[109]Markland, F.S. Snake venoms and the hemostatic system[J]. Toxicon,1998, (36):1749-1800.
[110]Yuan, C.-H., He, Q.-Y, Peng, K., Diao, J.-B., Jiang, L.-P., Tang, X., Liang, S.-P. Discovery of a Distinct Superfamily of Kunitz-Type Toxin (KTT) from Tarantulas[J]. PLoS ONE,2008, (3):e3414.
[111]Yang, N. & R. Horn, Evidence for voltage-dependent S4 movement in sodium channels[J]. Neuron,1995, (15):213-218.
[112]Li-Smerin, Y. & K.J. Swartz, Helical Structure of the Cooh Terminus of S3 and Its Contribution to the Gating Modifier Toxin Receptor in Voltage-Gated Ion Channels[J]. J. Gen. Physiol,2001, (117):205-218.
[113]Swartz, K.J. Sensing voltage across lipid membranes[J]. Nature,2008, (456): 891-897.
[114]Milescu, M., Bosmans, F., Lee, S., Alabi, A.A., Kim, J.I., Swartz, K.J. Interactions between lipids and voltage sensor paddles detected with tarantula toxins[J]. Nat. Struct. Mol. Biol,2009, (16):1080-1085.
[115]Catterall, W.A., Cestele, S., Yarov-Yarovoy, V, Yu, F.H., Konoki, K., Scheuer, T. Voltage-gated ion channels and gating modifier toxins[J]. Toxicon,2007, (49):124-141.
[116]Rodrl guez de la Vega, R.C., Merino, E., Becerril, B., Possani, L.D. Novel interactions between K+ channels and scorpion toxins[J]. Trends Pharmacol Sci,2003, (24):222-227.
[117]Swartz, K.J. Tarantula toxins interacting with voltage sensors in potassium channels[J]. Toxicon,2007, (49):213-230.
[118]Tytgat, J., Debont, T., Carmeliet, E., Daenens, P. The α-Dendrotoxin Footprint on a Mammalian Potassium Channel[J]. J. Biol. Chem,1995, (270): 24776-24781.
[119]Yeung, S.Y.M., Thompson, D., Wang, Z., Fedida, D., Robertson, B. Modulation of Kv3 Subfamily Potassium Currents by the Sea Anemone Toxin BDS:Significance for CNS and Biophysical Studies[J]. J. Neurosci, 2005, (25):8735-8745.
[120]Winterfield, J.R. & K.J. Swartz, A Hot Spot for the Interaction of Gating Modifier Toxins with Voltage-Dependent Ion Channels[J]. J. Gen. Physiol, 2000, (116):637-644.
[121]Li-Smerin, Y. & K.J. Swartz, Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels[J]. Proc. Natl. Acad. Sci. U.S.A,1998, (95):8585-8589.
[122]Liao, Z., Yuan, C., Peng, K., Xiao, Y., Liang, S. Solution structure of Jingzhaotoxin-III, a peptide toxin inhibiting both Navl.5 and Kv2.1 channels[J]. Toxicon,2007, (50):135-143.
[123]Rong, M., Chen, J., Tao, H., Wu, Y., Jiang, P., Lu, M., Su, H., Chi, Y, Cai, T., Zhao, L., Zeng, X., Xiao, Y, Liang, S. Molecular basis of the tarantula toxin jingzhaotoxin-Ⅲ (β-TRTX-Cj1α) interacting with voltage sensors in sodium channel subtype Nav1.5[J]. FASEB J,2011, (25):3177-3185.
[124]Nishizawa, M. & K. Nishizawa, Molecular Dynamics Simulations of a Stretch-Activated Channel Inhibitor GsMTx4 with Lipid Membranes:Two Binding Modes and Effects of Lipid Structure[J]. J Biophys,2007, (92): 4233-4243.
[125]Matsutomi, T., Nakamoto, C., Zheng, T., Kakimura, J.-i., Ogata, N. Multiple types of Na+ currents mediate action potential electrogenesis in small neurons of mouse dorsal root ganglia, Pfliigers Archiv[J]. Eur. J. Appl. Physiol,2006, (453):83-96.
[126]Bosmans, F. & K.J. Swartz, Targeting voltage sensors in sodium channels with spider toxins[J]. Trends Pharmacol Sci,2010, (31):175-182.
[127]Bosmans, F., Martin-Eauclaire, M.-F., Swartz, K.J. Deconstructing voltage sensor function and pharmacology in sodium channels[J]. Nature,2008, (456):202-208.
[128]Herrington, J., Zhou, Y.-P., Bugianesi, R.M., Dulski, P.M., Feng, Y., Warren, V.A., Smith, M.M., Kohler, M.G., Garsky, V.M., Sanchez, M., Wagner, M., Raphaelli, K., Banerjee, P., Ahaghotu, C., Wunderler, D., Priest, B.T., Mehl, J.T., Garcia, M.L., McManus, O.B., Kaczorowski, G.J., Slaughter, R.S. Blockers of the Delayed-Rectifier Potassium Current in Pancreatic β-Cells Enhance Glucose-Dependent Insulin Secretion[J]. Diabetes,2006, (55) 1034-1042.
[129]Melis, R., Stauffer, D., Zhao, X., Zhu, X.L., Albrecht, B., Pongs, O., Brothman, A., Leppert, M. Physical and genetic localization of a Shab subfamily potassium channel (KCNB1) gene to chromosomal region 20ql3.2[J]. Genomics,1995, (25):285-287.
[130]Misonou, H., Mohapatra, D.P., Menegola, M., Trimmer, J.S. Calcium- and Metabolic State-Dependent Modulation of the Voltage-Dependent Kv2.1 Channel Regulates Neuronal Excitability in Response to Ischemia[J]. J. Neurosci,2005, (25):11184-11193.
[131]Misonou, H., Thompson, S.M., Cai, X. Dynamic Regulation of the Kv2.1 Voltage-Gated Potassium Channel during Brain Ischemia through Neuroglial Interaction[J]. J. Neurosci,2008, (28):8529-8538.
[132]Ariano, M.A., Cepeda, C., Calvert, C.R., Flores-Hernandez, J., Hernandez-Echeagaray, E., Klapstein, G.J., Chandler, S.H., Aronin, N., DiFiglia, M., Levine, M.S. Striatal Potassium Channel Dysfunction in Huntington's Disease Transgenic Mice[J]. J. Neurophysiol,2005, (93): 2565-2574.
[133]Misonou, H., Mohapatra, D.P., Park, E.W., Leung, V, Zhen, D., Misonou, K., Anderson, A.E., Trimmer, J.S. Regulation of ion channel localization and phosphorylation by neuronal activity[J]. Nat Neurosci,2004, (7):711-718.
[134]Zhuang, G.-q., Wu, W., Liu, F., Ma, J.-l., Luo, Y.-x., Xiao, Z.-x., Liu, Y., Wang, W., He, Y. SNAP-251-180 enhances insulin secretion by blocking Kv2.1 channels in rat pancreatic islet P-cells[J]. Biochem. Biophys. Res. Commun, 2009, (379):812-816.
[135]Tamarina, N.A., Kuznetsov, A., Fridlyand, L.E., Philipson, L.H. Delayed-rectifier (KV2.1) regulation of pancreatic β-cell calcium responses to glucose:inhibitor specificity and modeling[J]. Am. J. Physiol. Endocrinol. Metab,2005, (289):E578-E585.
[136]Takahashi, H., Kim, J.I., Min, H.J., Sato, K., Swartz, K.J., Shimada, I. Solution structure of hanatoxinl, a gating modifier of voltage-dependent K+ channels: common surface features of gating modifier toxins[J]. J. Mol. Biol,2000, (297):771-780.
[137]Milescu, M., Vobecky, J., Roh, S.H., Kim, S.H., Jung, H.J., Kim, J.I., Swartz, K.J. Tarantula Toxins Interact with Voltage Sensors within Lipid Membranes[J]. J. Gen. Physiol,2007, (130):497-511.
[138]. Jung, H.H, Jung, H.J., Milescu, M., Lee, C.W., Lee, S., Lee, J.Y., Eu, Y.-J., Kim, H.H., Swartz, K.J., Kim, J.I. Structure and Orientation of a Voltage-Sensor Toxin in Lipid Membranes[J]. Biophys J,2010, (99): 638-646.
[139]Siemens, J., Zhou, S., Piskorowski, R., Nikai, T., Lumpkin, E.A., Basbaum, A.I., King, D., Julius, D. Spider toxins activate the capsaicin receptor to produce inflammatory pain[J]. Nature,2006, (444):208-212.
[140]Xiao, Y., Tang, J., Hu, W., Xie, J., Maertens, C., Tytgat, J., Liang, S. Jingzhaotoxin-Ⅰ, a Novel Spider Neurotoxin Preferentially Inhibiting Cardiac Sodium Channel Inactivation[J]. J Biol Chem,2005, (280):12069-12076.
[141]Deng, M., Kuang, F., Sun, Z., Tao, H., Cai, T., Zhong, L., Chen, Z., Xiao, Y., Liang, S. Jingzhaotoxin-IX, a novel gating modifier of both sodium and potassium channels from Chinese tarantula Chilobrachys jingzhao[J]. Neuropharmacology,2009, (57):77-87.
[142]Lee, S., Milescu, M., Jung, H.H., Lee, J.Y., Bae, C.H., Lee, C.W., Kim, H.H., Swartz, K.J., Kim, J.I. Solution Structure of GxTX-lE, a High-Affinity Tarantula Toxin Interacting with Voltage Sensors in Kv2.1 Potassium Channels[J]. Biochemistry,2010, (49):5134-5142.
[143]Yuan, C., Yang, S., Liao, Z., Liang, S. Effects and mechanism of Chinese Tarantula Toxins on the Kv2.1 potassium channels[J]. Biochem. Biophys. Res. Commun,2007, (352):799-804.
[144]Bemporad, D., Sands, Z.A., Wee, C.L., Grottesi, A., Sansom, M.S.P. Vstxl, a Modifier of Kv Channel Gating, Localizes to the Interfacial Region of Lipid Bilayers[J]. Biochemistry,2006, (45):11844-11855.
[145]Dib-Hajj, S.D., Binshtok, A.M., Cummins, T.R., Jarvis, M.F., Samad, T. Zimmermann, K. Voltage-gated sodium channels in pain states:Role in pathophysiology and targets for treatment[J]. Brain Res Rev,2009, (60): 65-83.
[146]Li, R.A. & G.F. Tomaselli. Using the deadly μ-conotoxins as probes of voltage-gated sodium channels[J]. Toxicon,2004, (44):117-122.
[147]Zhang, Y., Jiang, B., Li, W., Zhou, C., Ji, F., Xie, Q., Sun, X., An, L., Bao, Y. Mechanisms of Analgesic Action of Gln49-PLA from Gloydius ussurensis Snake Venom[J]. Appl. Biochem. Biotechnol,2010, (160):773-779.
[148]Ulbricht, W. Sodium Channel Inactivation:Molecular Determinants and Modulation[J]. Physiol. Rev,2005, (85):1271-1301.
[149]Ye, X., Bosmans, F., Li, C., Zhang, Y, Wang, D.-C., Tytgat, J. Structural Basis for the Voltage-gated Na+ Channel Selectivity of the Scorpion α-Like Toxin BmK M1. J[J]. Mol. Biol,2005, (353):788-803.
[150]Leipold, E., Lu, S., Gordon, D., Hansel, A., Heinemann, S.H. Combinatorial Interaction of Scorpion Toxins Lqh-2, Lqh-3, and LqhαIT with Sodium Channel Receptor Sites-3[J]. Mol. Pharmacol,2004, (65):685-691.
[151]Liu, L.-H., Bosmans, F., Maertens, C., Zhu, R.-H., Wang, D.-C., Tytgat, J. Molecular basis of the mammalian potency of the scorpion α-like toxin, BmK M1[J]. FASEB J.2005.
[152]Sokolov, S., Kraus, R.L., Scheuer, T., Catterall, W.A. Inhibition of Sodium Channel Gating by Trapping the Domain II Voltage Sensor with Protoxin II[J]. Mol. Pharmacol,2008, (73):1020-1028.
[153]Schmalhofer, W.A., Calhoun, J., Burrows, R., Bailey, T., Kohler, M.G., Weinglass, A.B., Kaczorowski, G.J., Garcia, M.L., Koltzenburg, M., Priest, B.T. ProTx-Ⅱ, a Selective Inhibitor of NaV1.7 Sodium Channels, Blocks Action Potential Propagation in Nociceptors[J]. Mol. Pharmacol,2008, (74):1476-1484.
[154]Zhang, X.-F., Shieh, C.-C, Chapman, M.L., Matulenko, M.A., Hakeem, A.H., Atkinson, R.N., Kort, M.E., Marron, B.E., Joshi, S., Honore, P., Faltynek, C.R., Krafte, D.S., Jarvis, M.F. A-887826 is a structurally novel, potent and voltage-dependent Navl.8 sodium channel blocker that attenuates neuropathic tactile allodynia in rats[J]. Neuropharmacology,2010, (59): 201-207.
[155]Zhu, M.-M., Tan, M., Cheng, H.-W., Ji, Y.-H. The a-like scorpion toxin BmK I enhances membrane excitability via persistent sodium current by preventing slow inactivation and deactivation of rNavl.2a expressed in Xenopus Oocytes[J]. Toxicol In Vitro,2009, (23):561-568.
[156]Nicholson, G.M., Little, M.J., Birinyi-Strachan, L.C. Structure and function of δ-atracotoxins:lethal neurotoxins targeting the voltage-gated sodium channel[J]. Toxicon,2004, (43):587-599.
[157]Yong Hua, J., Mansuelle, P., Terakawa, S., Kopeyan, C., Yanaihara, N., Ke, H., Rochat, H. Two neurotoxins (BmK Ⅰ and BmK Ⅱ) from the venom of the scorpion Buthus martensi Karsch:purification, amino acid sequences and assessment of specific activity[J]. Toxicon,1996, (34):987-1001.
[158]Wanke, E., Zaharenko, A.J., Redaelli, E., Schiavon, E. Actions of sea anemone type 1 neurotoxins on voltage-gated sodium channel isoforms[J]. Toxicon, 2009,(54):1102-1111.
[159]el-Sherif, N., Fozzard, H.A., Hanck, D.A. Dose-dependent modulation of the cardiac sodium channel by sea anemone toxin ATXII[J]. Circ. Res,1992, (70): 285-301.
[160]Gilles, N., Harrison, G., Karbat, I., Gurevitz, M., Nicholson, G.M., Gordon, D. Variations in receptor site-3 on rat brain and insect sodium channels highlighted by binding of a funnel-web spider δ-atracotoxin[J]. Eur J Biochem,2002, (269):1500-1510.
[161]Rogers, J.C., Qu, Y., Tanada, T.N., Scheuer, T., Catterall, W.A. Molecular Determinants of High Affinity Binding of a-Scorpion Toxin and Sea Anemone Toxin in the S3-S4 Extracellular Loop in Domain IV of the Na+ Channel a Subunit[J]. J Biol Chem,1996, (271):15950-15962.
[2]Rash, L.D. & W.C. Hodgson. Pharmacology and biochemistry of spider venoms[J]. Toxicon,2002,(40):225-254.
[3]Estrada, G., Villegas, E., Corzo, G. Spider venoms:a rich source of acylpolyamines and peptides as new leads for CNS drugs[J]. Nat Prod Rep, 2007,(24):145-161.
[4]Klint, J.K., Senff, S., Rupasinghe, D.B., Er, S.Y., Herzig, V., Nicholson, G.M., King, G.F. Spider-venom peptides that target voltage-gated sodium channels: Pharmacological tools and potential therapeutic leads[J]. Toxicon,2012, (60): 478-491.
[5]Sollod, B.L., Wilson, D., Zhaxybayeva, O., Gogarten, J.P., Drinkwater, R., King, GF. Were arachnids the first to use combinatorial peptide libraries? [J]. Peptides,2005, (26):131-139.
[6]Colgrave, M.L. & D.J. Craik.Thermal, Chemical, and Enzymatic Stability of the Cyclotide Kalata B1:□ The Importance of the Cyclic Cystine Knot[J]. Biochemistry,2004, (43):5965-5975.
[7]Chen, J.-Q., Zhang, Y.-Q., Dai, J., Luo, Z.-M., Liang, S.-P. Antinociceptive effects of intrathecally administered huwentoxin-I, a selective N-type calcium channel blocker, in the formalin test in conscious rats[J]. Toxicon, 2005,(45):15-20.
[8]Pinheiro, A.C.N., Gomez, R.S., Massensini, A.R., Cordeiro, M.N., Richardson, M., Romano-Silva, M.A., Prado, M.A.M., Marco, L.D., Gomez, M.V. Neuroprotective effect on brain injury by neurotoxins from the spider Phoneutria nigriventer[J]. Neurochem. Int,2006, (49):543-547.
[9]Isom, L., De Jongh, K., Patton, D., Reber, B., Offord, J., Charbonneau, H., Walsh, K., Goldin, A., Catterall, W. Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel [J]. Science,1992, (256):839-842.
[10]Isom, L.L., Ragsdale, D.S., De Jongh, K.S., Westenbroek, R.E., Reber, B.F.X., Scheuer, T., Catterall, W.A. Structure and function of the 22 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif[J]. Cell,1995, (83):433-442.
[11]Morgan, K., Stevens, E.B., Shah, B., Cox, P.J., Dixon, A.K., Lee, K., Pinnock, J. R.D., P.J. Hughes, K. Richardson, Jackson, A.P. β3:An additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics[J]. Proc. Natl. Acad. Sci. U.S.A,2000, (97): 2308-2313.
[12]Spampanato, J., Escayg, A., Meisler, M.H., Goldin, A.L. Generalized epilepsy with febrile seizures plus type 2 mutation W1204R alters voltage-dependent gating of Nav1.1 sodium channels[J]. Neuroscience,2003, (116):37-48.
[13]Chraibi, A., Schnizler, M., Clauss, W., Horisberger, J.D. Effects of 8-cpt-cAMP on the Epithelial Sodium Channel Expressed in Oocytes[J]. J. Membr. Biol, 2001,(183):15-23.
[14]Catterall, W. Structure and function of voltage-sensitive ion channels[J]. Science, 1988, (242):50-61.
[15]Saez, N.J., Senff, S., Jensen, J.E., Er, S.Y., Herzig, V., Rash, L.D., King, G.F. Spider-Venom Peptides as Therapeutics [J]. Toxins,2010, (2):2851-2871.
[16]Fletcher, J.I., Smith, R., Odonoghue, S.I., Nilges, M., Connor, M., Howden, M.J. Christie, M.E.H., King, G.F. The structure of a novel insecticidal neurotoxin, omega-atracotoxin-HV1, from the venom of an Australian funnel web spider[J]. Nat. Struct. Biol,1997, (5):59-66.
[17]Payandeh, J., Scheuer, T., Zheng, N., Catterall, W.A. The crystal structure of a voltage-gated sodium channel[J]. Nature,2011, (475):353-358.
[18]Yang, N., George, A.L., Horn, R. Molecular Basis of Charge Movement in Voltage-Gated Sodium Channels[J]. Neuron,1996, (16):113-122.
[19]Goldin, A.L. Mechanisms of sodium channel inactivation[J]. Cur Opinion in Neurobiology,2003, (13):284-290.
[20]Cestele, S., Scheuer, T., Mantegazza, M., Rochat, H., Catterall, W.A. Neutralization of Gating Charges in Domain Ⅱ of the Sodium Channel a Subunit Enhances Voltage-Sensor Trapping by a β-Scorpion Toxin[J]. J. Gen. Physiol,2001, (118):291-302.
[21]Catterall, W.A. From Ionic Currents to Molecular Mechanisms:The Structure and Function of Voltage-Gated Sodium Channels[J]. Neuron,2000, (26): 13-25.
[22]Penzotti, J.L., Fozzard, H.A., Lipkind, G.M., Dudley Jr, S.C. Differences in Saxitoxin and Tetrodotoxin Binding Revealed by Mutagenesis of the Na+ Channel Outer Vestibule[J]. Biophys J.1998, (75):2647-2657.
[23]Catterall, W.A. Structure and function of voltage-gated ion channels[J]. Trends Neurosci,1993, (16):500-506.
[24]Cestele, S., Catterall, W.A. Molecular mechanisms of neurotoxin action on voltage-gated sodium channels[J]. Biochimie,2000, (82):883-892.
[25]Isom, L.L. Sodium Channel β Subunits:Anything but Auxiliary[J]. Neuroscientist,2001, (7):42-54.
[26]Yu, F.H., Westenbroek, R.E., Silos-Santiago, I., McCormick, K.A., Lawson, D., Ge, P., Ferriera, H., Lilly, J., DiStefano, P.S., Catterall, W.A., Scheuer, T., Curtis, R. Sodium Channel β4, a New Disulfide-Linked Auxiliary Subunit with Similarity to β2[J]. J. Neurosci,2003, (23):7577-7585.
[27]Whitaker, W.R.J., Clare, J.J., Powell, A.J., Chen, Y.H., Faull, R.L.M., Emson, P.C. Distribution of voltage-gated sodium channel α-subunit and β-subunit mRNAs in human hippocampal formation, cortex, and cerebellum[J]. J. Comp. Neurol,2000, (422):123-139.
[28]Meadows, L., Malhotra, J.D., Stetzer, A., Isom, L.L., Ragsdale, D.S. The intracellular segment of the sodium channel β1 subunit is required for its efficient association with the channel a subunit[J]. J Neurochem,2001, (76): 1871-1878.
[29]Oh, Y., Sashihara, S., Black, J.A., Waxman, S.G. Na+ channel β1 subunit mRNA: differential expression in rat spinal sensory neurons[J]. Brain Res. Mol. Brain Res,1995, (30):357-361.
[30]Shah, B.S., Stevens, E.B., Gonzalez, M.I., Bramwell, S., Pinnock, R.D., Lee, K. Dixon, A.K. β3, a novel auxiliary subunit for the voltage-gated sodium channel, is expressed preferentially in sensory neurons and is upregulated in the chronic constriction injury model of neuropathic pain[J]. Eur J Neurosci, 2000, (12):3985-3990.
[31]Auld, V.J., Goldin, A.L., Krafte, D.S., Catterall, W.A., Lester, H.A., Davidson, N., Dunn, R.J. A neutral amino acid change in segment IIS4 dramatically alters the gating properties of the voltage-dependent sodium channel [J]. Proc. Nad. Acad. Sci. U.S.A,1990, (87):323-327.
[32]Rohl, C.A., Boeckman, F.A., Baker, C., Scheuer, T., Catterall, W.A., Klevit, R.E. Solution Structure of the Sodium Channel Inactivation Gate[J]. Biochemistry.1998, (38):855-861.
[33]Miyamoto, K., Nakagawa, T., Kuroda, Y., Kanaori, K. Solution structures of the inactivation gate particle peptides of rat brain type-IIA and human heart sodium channels in SDS micelles[J]. J. Pept. Res,2001, (57):203-214.
[34]Catterall, W.A., Goldin, A.L., Waxman, S.G. International Union of Pharmacology. XLVII. Nomenclature and Structure-Function Relationships of Voltage-Gated Sodium Channels[J]. Pharmacol. Rev,2005, (57):397-409.
[35]Catterall, W.A., Perez-Reyes, E., Snutch, T.P., Striessnig, J. International Union of Pharmacology. XLVIII. Nomenclature and Structure-Function Relationships of Voltage-Gated Calcium Channels[J]. Pharmacol. Rev,2005, (57):411-425.
[36]Ogata, N., Tatebayashi, H. Kinetic analysis of two types of Na+ channels in rat dorsal root ganglia[J]. J. Physio,1993, (466):9-37.
[37]Herzog, R.I., Liu, C., Waxman, S.G., Cummins, T.R. Calmodulin Binds to the C Terminus of Sodium Channels Nav1.4 and Navl.6 and Differentially Modulates Their Functional Properties[J]. J. Neurosci,2003, (23): 8261-8270.
[38]Maier, S.K.G., Westenbroek, R.E., Yamanushi, T.T., Dobrzynski, H., Boyett, M.R., Catterall, W.A., Scheuer, T. An unexpected requirement for brain-type sodium channels for control of heart rate in the mouse sinoatrial node[J]. Proc. Natl. Acad. Sci. U.S.A,2003, (100):3507-3512.
[39]Oda, A., Ohashi, H., Komori, S., Iida, H., Dohi, S. Characteristics of Ropivacaine Block of Na+ Channels in Rat Dorsal Root Ganglion Neurons[J]. Anesth. Analg,2000, (91):1213-1220.
[40]Lopreato, G.F., Lu, Y, Southwell, A., Atkinson, N.S., Hillis, D.M., Wilcox, T.P., Zakon, H.H. Evolution and divergence of sodium channel genes in vertebrates [J]. Proc. Natl. Acad. Sci. U.S.A,2001, (98):7588-7592.
[41]Goldin, A.L., Barchi, R.L., Caldwell, J.H., Hofmann, F., Howe, J.R., Hunter, J.C., Kallen, R.G., Mandel, G., Meisler, M.H., Netter, Y.B., Noda, M., Tamkun, M.M., Waxman, S.G., Wood, J.N. Catterall, W.A. Nomenclature of Voltage-Gated Sodium Channels[J]. Neuron,2000, (28): 365-368.
[42]Dib-Hajj, S.D., Black, J.A., Waxman, S.G. Voltage-Gated Sodium Channels: Therapeutic Targets for Pain[J]. Pain Medicine,2009, (10):1260-1269.
[43]Hains, B.C., Klein, J.P., Saab, C.Y., Craner, M.J., Black, J.A., Waxman, S.G. Upregulation of Sodium Channel Navl.3 and Functional Involvement in Neuronal Hyperexcitability Associated with Central Neuropathic Pain after Spinal Cord Injury[J]. J. Neurosci,2003, (23):8881-8892.
[44]Cummins, T.R., Dib-Hajj, S.D., Waxman, S.G. Electrophysiological Properties of Mutant Navl.7 Sodium Channels in a Painful Inherited Neuropathy[J]. J. Neurosci,2004, (24):8232-8236.
[45]Laird, J.M.A., Souslova, V, Wood, J.N., Cervero, F. Deficits in Visceral Pain and Referred Hyperalgesia in Navl.8 (SNS/PN3)-Null Mice[J]. J. Neurosci, 2002, (22):8352-8356.
[46]Escoubas, P., Diochot, S., Corzo, G. Structure and pharmacology of spider venom neurotoxins[J]. Biochimie,2000, (82):893-907.
[47]Smith, J.J., Blumenthal, K.M. Site-3 sea anemone toxins:Molecular probes of gating mechanisms in voltage-dependent sodium channels[J]. Toxicon,2007, (49):159-170.
[48]Hanck, D.A., Sheets, M.F. Site-3 toxins and cardiac sodium channels[J]. Toxicon,2007,(49):181-193.
[49]Nicholson, G.M., Walsh, R., Little, M.J., Tyler, M.I. Characterisation of the effects of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus on sodium channel activation and inactivation[J]. Eur. J. Physiol,1998,(436):117-126.
[50]Szeto, T.H., Birinyi-Strachan, L.C., Smith, R., Connor, M., Christie, M.J., King, G.F., Nicholson, G.M. Isolation and pharmacological characterisation of δ-atracotoxin-Hv1b, a vertebrate-selective sodium channel toxin[J]. FEBS Letters,2000, (470):293-299.
[51]Bosmans, F., Tytgat, J. Voltage-gated sodium channel modulation by scorpion α-toxins[J]. Toxicon,2007, (49):142-158.
[52]Goudet, C., Chi, C.-W., Tytgat, J. An overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch[J]. Toxicon,2002, (40): 1239-1258.
[53]Little, M.J., Wilson, H., Zappia, C., Cestele, S., Tyler, M.I., Martin-Eauclaire, M.-F., Gordon, D., Nicholson, G.M.δ-Atracotoxins from Australian funnel-web spiders compete with scorpion a-toxin binding on both rat brain and insect sodium channels[J]. FEBS Letters,1998, (439):246-252.
[54]Pallaghy, P.K., Norton, R.S., Nielsen, K.J., Craik, D.J. A common structural motif incorporating a cystine knot and a triple-stranded β-sheet in toxic and inhibitory polypeptides[J].Protein Sci,1994,(3):1833-1839.
[55]Corzo, G., Escoubas, P., Stankiewicz, M., Pelhate, M., Kristensen, C.P., Nakajima, T. Isolation, synthesis and pharmacological characterization of δ-palutoxins IT, novel insecticidal toxins from the spider Paracoelotes luctuosus (Amaurobiidae) [J]. Eur JBiochem,2000, (267):5783-5795.
[56]Skinner, W.S., Adams, M.E., Quistad, G.B., Kataoka, H., Cesarin, B.J., Enderlin, F.E., Schooley, D.A. Purification and characterization of two classes of neurotoxins from the funnel web spider, Agelenopsis aperta[J]. J Biol Chem, 1989, (264):2150-2155.
[57]Stapleton, A., Blankenship, D.T., Ackermann, B.L., Chen, T.M., Gorder, G.W., Manley, G.D., Palfreyman, M.G., Coutant, J.E., Cardin, A.D. Curtatoxins. Neurotoxic insecticidal polypeptides isolated from the funnel-web spider Hololena curta[J]. J Biol Chem,1990, (265):2054-2059.
[58]Matavel, A., Cruz, J.S., Penaforte, C.L., Araujo, D.A.M., Kalapothakis, E., Prado, V.F., Diniz, C.R., Cordeiro, M.N., Beirao, P.S.L. Electrophysiological characterization and molecular identification of the Phoneutria nigriventer peptide toxin PnTx2-6[J]. FEBS Letters,2002, (523):219-223.
[59]Sheumack, D.D., Claassens, R., Whiteley, N.M., Howden, M.H.H. Complete amino acid sequence of a new type of lethal neurotoxin from the venom of the funnel-web spider Atrax robustus[J]. FEBS Letters,1985, (181):154-156.
[60]Little, M.J., Zappia, C., Gilles, N., Connor, M., Tyler, M.I., Martin-Eauclaire, M.-F., Gordon, D., Nicholson, G.M.8-Atracotoxins from Australian Funnel-web Spiders Compete with Scorpion α-Toxin Binding but Differentially Modulate Alkaloid Toxin Activation of Voltage-gated Sodium Channels[J]. J Biol Chem,1998, (273):27076-27083.
[61]Calegario Oliveira, L., De Lima, M.E., Pimenta, A.M.C., Mansuelle, P., Rochat, H., Cordeiro, M.N., Richardson, M., Figueiredo, S.G. PnTx4-3, a new insect toxin from Phoneutria nigriventer venom elicits the glutamate uptake inhibition exhibited by PhTx4 toxic fraction[J]. Toxicon,2003, (42):793-800.
[62]Wang, M., Liu, Q., Luo, H., Li, J., Tang, J., Xiao, Y, Liang, S. Jingzhaotoxin-Ⅱ, a novel tarantula toxin preferentially targets rat cardiac sodium channel [J]. Biochem Pharmacol,2008, (76):1716-1727.
[63]Cestele, S., Qu, Y., Rogers, J.C., Rochat, H., Scheuer, T., Catterall, W.A. Voltage Sensor Trapping:Enhanced Activation of Sodium Channels by 2-Scorpion Toxin Bound to the S3 S4 Loop in Domain II[J]. Neuron,1998, (21):919-931.
[64]Cestele, S., Yarov-Yarovoy, V., Qu, Y, Sampieri, F., Scheuer, T., Catterall, W.A. Structure and Function of the Voltage Sensor of Sodium Channels Probed by a β-Scorpion Toxin[J]. J Biol Chem,2006, (281):21332-21344.
[65]Middleton, R.E., Warren, V.A., Kraus, R.L., Hwang, J.C., Liu, C.J., Dai, G., Brochu, R.M., Kohler, M.G., Gao, Y.-D., Garsky, V.M., Bogusky, M.J., Mehl, J.T., Cohen, C.J., Smith, M.M. Two Tarantula Peptides Inhibit Activation of Multiple Sodium Channels[J]. Biochemistry,2002, (41):14734-14747.
[66]Priest, B.T., Blumenthal, K.M., Smith, J.J., Warren, V.A., Smith, M.M. ProTx-Ⅰ and ProTx-Ⅱ:Gating modifiers of voltage-gated sodium channels[J]. Toxicon, (49):194-201.
[67]Xiao, Y, Luo, X., Kuang, F., Deng, M., Wang, M., Zeng, X., Liang, S. Synthesis and characterization of huwentoxin-IV, a neurotoxin inhibiting central neuronal sodium channels[J]. Toxicon,2008, (51):230-239.
[68]Wolfner, M.F., Harada, H.A., Bertram, M.J., Stelick, T.J., Kraus, K.W., Kalb, J.M., Lung, Y.O., Neubaum, D.M., Park, M., Tram, U. New Genes for Male Accessory Gland Proteins in Drosophila melanogaster[J]. Insect Biochem. Mol. Biol,1997, (27):825-834.
[69]Corzo, G., Sabo, J.K., Bosmans, F., Billen, B., Villegas, E., Tytgat, J., Norton, R.S. Solution Structure and Alanine Scan of a Spider Toxin That Affects the Activation of Mammalian Voltage-gated Sodium Channels[J]. J Biol Chem, 2007, (282):4643-4652.
[70]Xiao, Y, Tang, J., Yang, Y, Wang, M., Hu, W., Xie, J., Zeng, X., Liang, S. Jingzhaotoxin-Ⅲ, a Novel Spider Toxin Inhibiting Activation of Voltage-gated Sodium Channel in Rat Cardiac Myocytes[J]. J. Biol. Chem, 2004, (279):26220-26226.
[71]Corzo, G., Gilles, N., Satake, H., Villegas, E., Dai, L., Nakajima, T., Haupt, J. Distinct primary structures of the major peptide toxins from the venom of the spider Macrothele gigas that bind to sites 3 and 4 in the sodium channel[J]. FEBS Letters,2003, (547):43-50.
[72]Peng, K., Shu, Q., Liu, Z., Liang, S. Function and Solution Structure of Huwentoxin-Ⅳ, a Potent Neuronal Tetrodotoxin (TTX)-sensitive Sodium Channel Antagonist from Chinese Bird Spider Selenocosmia huwena[J]. J. Biol. Chem,2002, (277):47564-47571.
[73]Coetzee, W.A., Amarillo, Y., Chiu, J., Chow, A., Lau, D., McCormack, T.O.M., Morena, H., Nadal, M.S., Ozaita, A., Pountney, D., Saganich, M., De Miera, E.V.-S., Rudy, B. Molecular Diversity of K+ Channels [J]. Ann. Ny Acad. Sci,1999,(868):233-255.
[74]Lu, Z., Klem, A.M., Ramu, Y. Ion conduction pore is conserved among potassium channels[J]. Nature,2001, (413):809-813.
[75]Jiang, Y., Lee, A., Chen, J., Ruta, V., Cadene, M., Chait, B.T., MacKinnon, R. X-ray structure of a voltage-dependent K+ channel[J]. Nature,2003, (423): 33-41.
[76]Long, S.B., Tao, X., Campbell, E.B., MacKinnon, R. Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment[J]. Nature,2007, (450):376-382.
[77]Corzo, G., Papp, F., Varga, Z., Barraza, O., Espino-Solis, P.G., Rodriguez de la Vega, R.C., Gaspar, R., Panyi, G., Possani, L.D. A selective blocker of Kvl.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus[J]. Biochem Pharmacol,2008, (76):1142-1154.
[78]Ruta, V., Jiang, Y., Lee, A., Chen, J., MacKinnon, R. Functional analysis of an archaebacterial voltage-dependent K+ channel[J]. Nature,2003, (422): 180-185.
[79]Miller, C. See potassium run[J]. Nature,2001, (414):23-24.
[80]Doyle, D.A., Cabral, J.M., Pfuetzner, R.A., Kuo, A., Gulbis, J.M., Cohen, S.L Chait, B.T., MacKinnon, R. The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity[J]. Science,1998, (280): 69-77.
[81]Long, S.B., Campbell, E.B., MacKinnon, R. Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel[J]. Science,2005, (309): 897-903.
[82]Shieh, C.-C., Coghlan, M., Sullivan, J.P., Gopalakrishnan, M. Potassium Channels:Molecular Defects, Diseases, and Therapeutic Opportunities [J]. Pharmacol. Rev,2000, (52):557-594.
[83]Schweitz, H., Bruhn, T., Guillemare, E., Moinier, D., Lancelin, J.-M., Beress, L., Lazdunski, M., Kalicludines and Kaliseptine[J]. J Biol Chem,1995, (270): 25121-25126.
[84]Escoubas, P., Diochot, S., Celerier, M.-L., Nakajima, T., Lazdunski, M. Novel Tarantula Toxins for Subtypes of Voltage-Dependent Potassium Channels in the Kv2 and Kv4 Subfamilies[J]. Mol. Pharmacol.2002, (62):48-57.
[85]Wang, F.C., Bell, N., Reid, P., Smith, L.A., McIntosh, P., Robertson, B., Dolly, J.O. Identification of residues in dendrotoxin K responsible for its discrimination between neuronal K+ channels containing Kv1.1 and 1.2 a subunits[J]. Eur J Bioche,1999, (263):222-229.
[86]Lee, C.W., Kim, S., Roh, S.H., Endoh, H., Kodera, Y, Maeda, T., Kohno, T., Wang, J.M., Swartz, K.J., Kim, J.I. Solution Structure and Functional Characterization of SGTx1, a Modifier of Kv2.1 Channel Gating[J]. Biochemistry,2004, (43):890-897.
[87]Takahashi, H., Kim, J.I., Min, H.J., Sato, K., Swartz, K.J., Shimada, I. Solution structure of hanatoxin1, a gating modifier of voltage-dependent K+ channels: common surface features of gating modifier toxins[J]. J. Mol. Biol,2000, (297):771-780.
[88]Oswald, R.E., Suchyna, T.M., McFeeters, R., Gottlieb, P., Sachs, F. Solution Structure of Peptide Toxins That Block Mechanosensitive Ion Channels[J]. J Biol Chem,2002, (277):34443-34450.
[89]Swartz, K.J., MacKinnon, R. An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula[J]. Neuron,1995, (15): 941-949.
[90]Lee, H.C., Wang, J.M., Swartz, K.J. Interaction between Extracellular Hanatoxin and the Resting Conformation of the Voltage-Sensor Paddle in Kv Channels[J]. Neuron,2003, (40):527-536.
[91]Swartz, K.J. & R. MacKinnon. Mapping the Receptor Site for Hanatoxin, a Gating Modifier of Voltage-Dependent K+ Channels[J]. Neuron,1997, (18): 675-682.
[92]Li-Smerin, Y. & K.J. Swartz. Localization and Molecular Determinants of the Hanatoxin Receptors on the Voltage-Sensing Domains of a K+ Channel[J]. J. Gen. Physiol,2000, (115):673-684.
[93]Revell Phillips, L., Milescu, M., Li-Smerin, Y., Mindell, J.A., Kim, J.I., Swartz, K.J. Voltage-sensor activation with a tarantula toxin as cargo[J]. Nature,2005, (436):857-860.
[94]Marvin, L., De, E., Cosette, P., Gagnon, J., Molle, G., Lange, C. Isolation, amino acid sequence and functional assays of SGTx1[J]. Eur J Biochem, 1999, (265):572-579.
[95]Wang, J.M., Roh, S.H., Kim, S., Lee, C.W., Kim, J.I., Swartz, K.J. Molecular Surface of Tarantula Toxins Interacting with Voltage Sensors in Kv Channels[J].J. Gen. Physiol,2004, (123):455-467.
[96]Zarayskiy, V.V., Balasubramanian, G, Bondarenko, V.E., Morales, M.J. Heteropoda toxin 2 is a gating modifier toxin specific for voltage-gated K+ channels of the Kv4 family[J]. Toxicon,2005, (45):431-442.
[97]DeSimone, C.V., Zarayskiy, V.V., Bondarenko, V.E., Morales, M.J. Heteropoda Toxin 2 Interaction with Kv4.3 and Kv4.1 Reveals Differences in Gating Modification[J]. Mol. Pharmacol,2011, (80):345-355.
[98]DeSimone, C.V., Lu, Y., Bondarenko, V.E., Morales, M.J. S3b Amino Acid Substitutions and Ancillary Subunits Alter the Affinity of Heteropoda venatoria Toxin 2 for Kv4.3[J]. Mol. Pharmacol,2009, (76):125-133.
[99]Sanguinetti, M.C., Johnson, J.H., Hammerland, L.G., Kelbaugh, P.R., Volkmann, R.A., Saccomano, N.A., Mueller, A.L. Heteropodatoxins:Peptides Isolated from Spider Venom that Block Kv4.2 Potassium Channels[J]. Mol. Pharmacol,1997, (51):491-498.
[100]Lee, S.-Y. & R. MacKinnon, A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom[J]. Nature,2004. (430):232-235.
[101]Liao, Z., Yuan, C. Deng, M., Li, J., Chen, J., Yang, Y., Hu, W., Liang, S. Solution Structure and Functional Characterization of Jingzhaotoxin-Ⅺ:□ A Novel Gating Modifier of both Potassium and Sodium Channels[J]. Biochemistry,2006, (45):15591-15600.
[102]Yuan, C., Liao, Z., Zeng, X., Dai, L., Kuang, F., Liang, S. Jingzhaotoxin-XII, a gating modifier specific for Kv4.1 channels[J]. Toxicon,2007, (50):646-652.
[103]Zeng, X., Deng, M., Lin, Y, Yuan, C., Pi, J., Liang, S. Isolation and characterization of Jingzhaotoxin-V, a novel neurotoxin from the venom of the spider Chilobrachys jingzhao[J]. Toxicon,2007, (49):388-399.
[104]Jung, H.J., Lee, J.Y, Kim, S.H., Eu, Y.-J., Shin, S.Y, Milescu, M., Swartz, K.J., Kim, J.I. Solution Structure and Lipid Membrane Partitioning of VSTx1, an Inhibitor of the KvAP Potassium Channel[J]. Biochemistry,2005, (44): 6015-6023.
[105]Yuan, C., Jin, Q., Tang, X., Hu, W., Cao, R., Yang, S., Xiong, J., Xie, C., Xie, J., Liang, S. Proteomic and Peptidomic Characterization of the Venom from the Chinese Bird Spider, Ornithoctonus huwena Wang[J]. J. Proteome Res, 2007, (6):2792-2801.
[106]Tang, X., Zhang, Y, Hu, W., Xu, D., Tao, H., Yang, X., Li, Y, Jiang, L., Liang, S. Molecular Diversification of Peptide Toxins from the Tarantula Haplopelma hainanum (Ornithoctonus hainana) Venom Based on Transcriptomic, Peptidomic, and Genomic Analyses[J]. J. Proteome Res, 2010, (9):2550-2564.
[107]Liao, Z., Cao, J., Li, S., Yan, X., Hu, W., He, Q., Chen, J., Tang, J., Xie, J., Liang, S. Proteomic and peptidomic analysis of the venom from Chinese tarantula Chilobrachys jingzhao[J]. Proteomics,2007, (7):1892-1907.
[108]Suchyna, T.M., Tape, S.E., Koeppe, R.E., Andersen, O.S., Sachs, F., Gottlieb, P.A. Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers[J]. Nature,2004, (430):235-240.
[109]Markland, F.S. Snake venoms and the hemostatic system[J]. Toxicon,1998, (36):1749-1800.
[110]Yuan, C.-H., He, Q.-Y, Peng, K., Diao, J.-B., Jiang, L.-P., Tang, X., Liang, S.-P. Discovery of a Distinct Superfamily of Kunitz-Type Toxin (KTT) from Tarantulas[J]. PLoS ONE,2008, (3):e3414.
[111]Yang, N. & R. Horn, Evidence for voltage-dependent S4 movement in sodium channels[J]. Neuron,1995, (15):213-218.
[112]Li-Smerin, Y. & K.J. Swartz, Helical Structure of the Cooh Terminus of S3 and Its Contribution to the Gating Modifier Toxin Receptor in Voltage-Gated Ion Channels[J]. J. Gen. Physiol,2001, (117):205-218.
[113]Swartz, K.J. Sensing voltage across lipid membranes[J]. Nature,2008, (456): 891-897.
[114]Milescu, M., Bosmans, F., Lee, S., Alabi, A.A., Kim, J.I., Swartz, K.J. Interactions between lipids and voltage sensor paddles detected with tarantula toxins[J]. Nat. Struct. Mol. Biol,2009, (16):1080-1085.
[115]Catterall, W.A., Cestele, S., Yarov-Yarovoy, V, Yu, F.H., Konoki, K., Scheuer, T. Voltage-gated ion channels and gating modifier toxins[J]. Toxicon,2007, (49):124-141.
[116]Rodrl guez de la Vega, R.C., Merino, E., Becerril, B., Possani, L.D. Novel interactions between K+ channels and scorpion toxins[J]. Trends Pharmacol Sci,2003, (24):222-227.
[117]Swartz, K.J. Tarantula toxins interacting with voltage sensors in potassium channels[J]. Toxicon,2007, (49):213-230.
[118]Tytgat, J., Debont, T., Carmeliet, E., Daenens, P. The α-Dendrotoxin Footprint on a Mammalian Potassium Channel[J]. J. Biol. Chem,1995, (270): 24776-24781.
[119]Yeung, S.Y.M., Thompson, D., Wang, Z., Fedida, D., Robertson, B. Modulation of Kv3 Subfamily Potassium Currents by the Sea Anemone Toxin BDS:Significance for CNS and Biophysical Studies[J]. J. Neurosci, 2005, (25):8735-8745.
[120]Winterfield, J.R. & K.J. Swartz, A Hot Spot for the Interaction of Gating Modifier Toxins with Voltage-Dependent Ion Channels[J]. J. Gen. Physiol, 2000, (116):637-644.
[121]Li-Smerin, Y. & K.J. Swartz, Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels[J]. Proc. Natl. Acad. Sci. U.S.A,1998, (95):8585-8589.
[122]Liao, Z., Yuan, C., Peng, K., Xiao, Y., Liang, S. Solution structure of Jingzhaotoxin-III, a peptide toxin inhibiting both Navl.5 and Kv2.1 channels[J]. Toxicon,2007, (50):135-143.
[123]Rong, M., Chen, J., Tao, H., Wu, Y., Jiang, P., Lu, M., Su, H., Chi, Y, Cai, T., Zhao, L., Zeng, X., Xiao, Y, Liang, S. Molecular basis of the tarantula toxin jingzhaotoxin-Ⅲ (β-TRTX-Cj1α) interacting with voltage sensors in sodium channel subtype Nav1.5[J]. FASEB J,2011, (25):3177-3185.
[124]Nishizawa, M. & K. Nishizawa, Molecular Dynamics Simulations of a Stretch-Activated Channel Inhibitor GsMTx4 with Lipid Membranes:Two Binding Modes and Effects of Lipid Structure[J]. J Biophys,2007, (92): 4233-4243.
[125]Matsutomi, T., Nakamoto, C., Zheng, T., Kakimura, J.-i., Ogata, N. Multiple types of Na+ currents mediate action potential electrogenesis in small neurons of mouse dorsal root ganglia, Pfliigers Archiv[J]. Eur. J. Appl. Physiol,2006, (453):83-96.
[126]Bosmans, F. & K.J. Swartz, Targeting voltage sensors in sodium channels with spider toxins[J]. Trends Pharmacol Sci,2010, (31):175-182.
[127]Bosmans, F., Martin-Eauclaire, M.-F., Swartz, K.J. Deconstructing voltage sensor function and pharmacology in sodium channels[J]. Nature,2008, (456):202-208.
[128]Herrington, J., Zhou, Y.-P., Bugianesi, R.M., Dulski, P.M., Feng, Y., Warren, V.A., Smith, M.M., Kohler, M.G., Garsky, V.M., Sanchez, M., Wagner, M., Raphaelli, K., Banerjee, P., Ahaghotu, C., Wunderler, D., Priest, B.T., Mehl, J.T., Garcia, M.L., McManus, O.B., Kaczorowski, G.J., Slaughter, R.S. Blockers of the Delayed-Rectifier Potassium Current in Pancreatic β-Cells Enhance Glucose-Dependent Insulin Secretion[J]. Diabetes,2006, (55) 1034-1042.
[129]Melis, R., Stauffer, D., Zhao, X., Zhu, X.L., Albrecht, B., Pongs, O., Brothman, A., Leppert, M. Physical and genetic localization of a Shab subfamily potassium channel (KCNB1) gene to chromosomal region 20ql3.2[J]. Genomics,1995, (25):285-287.
[130]Misonou, H., Mohapatra, D.P., Menegola, M., Trimmer, J.S. Calcium- and Metabolic State-Dependent Modulation of the Voltage-Dependent Kv2.1 Channel Regulates Neuronal Excitability in Response to Ischemia[J]. J. Neurosci,2005, (25):11184-11193.
[131]Misonou, H., Thompson, S.M., Cai, X. Dynamic Regulation of the Kv2.1 Voltage-Gated Potassium Channel during Brain Ischemia through Neuroglial Interaction[J]. J. Neurosci,2008, (28):8529-8538.
[132]Ariano, M.A., Cepeda, C., Calvert, C.R., Flores-Hernandez, J., Hernandez-Echeagaray, E., Klapstein, G.J., Chandler, S.H., Aronin, N., DiFiglia, M., Levine, M.S. Striatal Potassium Channel Dysfunction in Huntington's Disease Transgenic Mice[J]. J. Neurophysiol,2005, (93): 2565-2574.
[133]Misonou, H., Mohapatra, D.P., Park, E.W., Leung, V, Zhen, D., Misonou, K., Anderson, A.E., Trimmer, J.S. Regulation of ion channel localization and phosphorylation by neuronal activity[J]. Nat Neurosci,2004, (7):711-718.
[134]Zhuang, G.-q., Wu, W., Liu, F., Ma, J.-l., Luo, Y.-x., Xiao, Z.-x., Liu, Y., Wang, W., He, Y. SNAP-251-180 enhances insulin secretion by blocking Kv2.1 channels in rat pancreatic islet P-cells[J]. Biochem. Biophys. Res. Commun, 2009, (379):812-816.
[135]Tamarina, N.A., Kuznetsov, A., Fridlyand, L.E., Philipson, L.H. Delayed-rectifier (KV2.1) regulation of pancreatic β-cell calcium responses to glucose:inhibitor specificity and modeling[J]. Am. J. Physiol. Endocrinol. Metab,2005, (289):E578-E585.
[136]Takahashi, H., Kim, J.I., Min, H.J., Sato, K., Swartz, K.J., Shimada, I. Solution structure of hanatoxinl, a gating modifier of voltage-dependent K+ channels: common surface features of gating modifier toxins[J]. J. Mol. Biol,2000, (297):771-780.
[137]Milescu, M., Vobecky, J., Roh, S.H., Kim, S.H., Jung, H.J., Kim, J.I., Swartz, K.J. Tarantula Toxins Interact with Voltage Sensors within Lipid Membranes[J]. J. Gen. Physiol,2007, (130):497-511.
[138]. Jung, H.H, Jung, H.J., Milescu, M., Lee, C.W., Lee, S., Lee, J.Y., Eu, Y.-J., Kim, H.H., Swartz, K.J., Kim, J.I. Structure and Orientation of a Voltage-Sensor Toxin in Lipid Membranes[J]. Biophys J,2010, (99): 638-646.
[139]Siemens, J., Zhou, S., Piskorowski, R., Nikai, T., Lumpkin, E.A., Basbaum, A.I., King, D., Julius, D. Spider toxins activate the capsaicin receptor to produce inflammatory pain[J]. Nature,2006, (444):208-212.
[140]Xiao, Y., Tang, J., Hu, W., Xie, J., Maertens, C., Tytgat, J., Liang, S. Jingzhaotoxin-Ⅰ, a Novel Spider Neurotoxin Preferentially Inhibiting Cardiac Sodium Channel Inactivation[J]. J Biol Chem,2005, (280):12069-12076.
[141]Deng, M., Kuang, F., Sun, Z., Tao, H., Cai, T., Zhong, L., Chen, Z., Xiao, Y., Liang, S. Jingzhaotoxin-IX, a novel gating modifier of both sodium and potassium channels from Chinese tarantula Chilobrachys jingzhao[J]. Neuropharmacology,2009, (57):77-87.
[142]Lee, S., Milescu, M., Jung, H.H., Lee, J.Y., Bae, C.H., Lee, C.W., Kim, H.H., Swartz, K.J., Kim, J.I. Solution Structure of GxTX-lE, a High-Affinity Tarantula Toxin Interacting with Voltage Sensors in Kv2.1 Potassium Channels[J]. Biochemistry,2010, (49):5134-5142.
[143]Yuan, C., Yang, S., Liao, Z., Liang, S. Effects and mechanism of Chinese Tarantula Toxins on the Kv2.1 potassium channels[J]. Biochem. Biophys. Res. Commun,2007, (352):799-804.
[144]Bemporad, D., Sands, Z.A., Wee, C.L., Grottesi, A., Sansom, M.S.P. Vstxl, a Modifier of Kv Channel Gating, Localizes to the Interfacial Region of Lipid Bilayers[J]. Biochemistry,2006, (45):11844-11855.
[145]Dib-Hajj, S.D., Binshtok, A.M., Cummins, T.R., Jarvis, M.F., Samad, T. Zimmermann, K. Voltage-gated sodium channels in pain states:Role in pathophysiology and targets for treatment[J]. Brain Res Rev,2009, (60): 65-83.
[146]Li, R.A. & G.F. Tomaselli. Using the deadly μ-conotoxins as probes of voltage-gated sodium channels[J]. Toxicon,2004, (44):117-122.
[147]Zhang, Y., Jiang, B., Li, W., Zhou, C., Ji, F., Xie, Q., Sun, X., An, L., Bao, Y. Mechanisms of Analgesic Action of Gln49-PLA from Gloydius ussurensis Snake Venom[J]. Appl. Biochem. Biotechnol,2010, (160):773-779.
[148]Ulbricht, W. Sodium Channel Inactivation:Molecular Determinants and Modulation[J]. Physiol. Rev,2005, (85):1271-1301.
[149]Ye, X., Bosmans, F., Li, C., Zhang, Y, Wang, D.-C., Tytgat, J. Structural Basis for the Voltage-gated Na+ Channel Selectivity of the Scorpion α-Like Toxin BmK M1. J[J]. Mol. Biol,2005, (353):788-803.
[150]Leipold, E., Lu, S., Gordon, D., Hansel, A., Heinemann, S.H. Combinatorial Interaction of Scorpion Toxins Lqh-2, Lqh-3, and LqhαIT with Sodium Channel Receptor Sites-3[J]. Mol. Pharmacol,2004, (65):685-691.
[151]Liu, L.-H., Bosmans, F., Maertens, C., Zhu, R.-H., Wang, D.-C., Tytgat, J. Molecular basis of the mammalian potency of the scorpion α-like toxin, BmK M1[J]. FASEB J.2005.
[152]Sokolov, S., Kraus, R.L., Scheuer, T., Catterall, W.A. Inhibition of Sodium Channel Gating by Trapping the Domain II Voltage Sensor with Protoxin II[J]. Mol. Pharmacol,2008, (73):1020-1028.
[153]Schmalhofer, W.A., Calhoun, J., Burrows, R., Bailey, T., Kohler, M.G., Weinglass, A.B., Kaczorowski, G.J., Garcia, M.L., Koltzenburg, M., Priest, B.T. ProTx-Ⅱ, a Selective Inhibitor of NaV1.7 Sodium Channels, Blocks Action Potential Propagation in Nociceptors[J]. Mol. Pharmacol,2008, (74):1476-1484.
[154]Zhang, X.-F., Shieh, C.-C, Chapman, M.L., Matulenko, M.A., Hakeem, A.H., Atkinson, R.N., Kort, M.E., Marron, B.E., Joshi, S., Honore, P., Faltynek, C.R., Krafte, D.S., Jarvis, M.F. A-887826 is a structurally novel, potent and voltage-dependent Navl.8 sodium channel blocker that attenuates neuropathic tactile allodynia in rats[J]. Neuropharmacology,2010, (59): 201-207.
[155]Zhu, M.-M., Tan, M., Cheng, H.-W., Ji, Y.-H. The a-like scorpion toxin BmK I enhances membrane excitability via persistent sodium current by preventing slow inactivation and deactivation of rNavl.2a expressed in Xenopus Oocytes[J]. Toxicol In Vitro,2009, (23):561-568.
[156]Nicholson, G.M., Little, M.J., Birinyi-Strachan, L.C. Structure and function of δ-atracotoxins:lethal neurotoxins targeting the voltage-gated sodium channel[J]. Toxicon,2004, (43):587-599.
[157]Yong Hua, J., Mansuelle, P., Terakawa, S., Kopeyan, C., Yanaihara, N., Ke, H., Rochat, H. Two neurotoxins (BmK Ⅰ and BmK Ⅱ) from the venom of the scorpion Buthus martensi Karsch:purification, amino acid sequences and assessment of specific activity[J]. Toxicon,1996, (34):987-1001.
[158]Wanke, E., Zaharenko, A.J., Redaelli, E., Schiavon, E. Actions of sea anemone type 1 neurotoxins on voltage-gated sodium channel isoforms[J]. Toxicon, 2009,(54):1102-1111.
[159]el-Sherif, N., Fozzard, H.A., Hanck, D.A. Dose-dependent modulation of the cardiac sodium channel by sea anemone toxin ATXII[J]. Circ. Res,1992, (70): 285-301.
[160]Gilles, N., Harrison, G., Karbat, I., Gurevitz, M., Nicholson, G.M., Gordon, D. Variations in receptor site-3 on rat brain and insect sodium channels highlighted by binding of a funnel-web spider δ-atracotoxin[J]. Eur J Biochem,2002, (269):1500-1510.
[161]Rogers, J.C., Qu, Y., Tanada, T.N., Scheuer, T., Catterall, W.A. Molecular Determinants of High Affinity Binding of a-Scorpion Toxin and Sea Anemone Toxin in the S3-S4 Extracellular Loop in Domain IV of the Na+ Channel a Subunit[J]. J Biol Chem,1996, (271):15950-15962.