BK通道门控、转运和结合位点的研究
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摘要
离子通道作为一种膜蛋白在动物、植物、单细胞或多细胞生物的细胞膜上广泛存在,产生细胞生物电现象。钙依赖、电压激活的大电导钾通道(BK通道)作为钾离子通道家族中的一员,在线虫、昆虫和哺乳动物的肌肉、脑、胰腺、背根神经节上都有表达。BK通道的α亚基不同剪接变体和四种β亚基一起促成了其电流和功能的多样性。
β2亚基通过其N端的三个疏水性氨基酸FIW产生了失活的BK电流。本文以BK通道β2亚基为研究对象,以HEK293细胞为工具,利用免疫荧光技术,共聚焦显微镜技术,结合分子生物学和电生理学方法,研究了β2亚基的转运机制,探索了其与α亚基的结合位点。主要内容如下:
(1)通过在β2的N端增加三个疏水性的氨基酸FIW(dFIW),我们发现没有记录到预期的失活加强的BK电流,而是记录不到任何电流。通过荧光实验我们发现这种突变体dFIW造成了其本身和共表达的α亚基的ER滞留。通过突变其N端的带电荷的氨基酸D16E17和E44D45,我们发现突变体E44D45能使大部分的α亚基上膜,同时能记录到没有失活的BK电流。我们推断E44D45是结合位点之一。
(2)通过在β2亚基的胞外部分加入抗原决定簇c-myc,利用荧光素耦联的抗体检测发现β2亚基不同于β1亚基,它单独不能被运输到HEK细胞膜上,而是被滞留在内质网(ER)。但与α亚基共表达可以被α亚基带上膜。通过切掉其N端或C端的一些序列我们发现β2亚基N端的一段α螺旋(18-31)造成了其ER滞留。通过在其loop的不同位置加抗原,我们发现K137附近是最容易被抗体接近的区域。
小鼠mslo1形成的BK单通道电流有较长的开放,但线虫dslo(A2/C2/E2/G5/10)在开放时却非常flickery。本文还以BK通道α亚基为研究对象,以非洲爪蟾卵母细胞为工具,利用电生理技术研究BK通道的门控机制。主要内容如下:
我们发现mSlo的突变体I323T会产生跟dslo(A2/C2/E2/G5/10)类似快速开放的单通道电导,并且还有外向整流的性质。而突变dslo(A2/C2/E2/G5/10)相应位置的亲水性氨基酸T337I,发现该通道开放的单通道电导不再flickery。通过单通道电导分析我们发现突变体I323T存在不同亚态的亚电导,这是因为四个亚基之间的协同性被破坏造成的。通过对mSlo的I323位点做一系列的突变,我们发现越疏水性的氨基酸会产生越长的单通道电导。分子动力学模拟表明位于BK通道孔道的四个疏水性氨基酸I323在通道门控过程中起着“开关”作用。因此,我们证明BK通道的亚电导是由于323位置的四个氨基酸残基的协同性降低和开放几率的降低造成的。
Large-conductance voltage- and Ca2+-activated K+ (BK) channels encoded by the msloαandβ2 subunits exist abundantly in rat chromaffin cells, pancreaticβcells and DRG neurons. The extracellular loop of hβ2 acting as the channel regulator influences the rectification and toxin sensitivity of BK channels and the inactivation domain at its N-terminus induces rapid inactivation. However, the regulatory mechanism, especially, the trafficking mechanism of hβ2 is still unknown. With the help of immunofluorescence and patch-clamp techniques, we found that the hβ2 subunit could be completely restrained within the cytoplast of cells by inserting three amino acids FIW at the upstream of its N-terminus termed double FIW or dFIW-hβ2. The dFIW-hβ2 also prevented mSloαsubunit from trafficking onto membrane surface and thus suppressed BK currents to null. Consequently, a novel method has been developed to identify the binding sites between the mSloαand hβ2 subunits of BK channels in this study. Our results reveal that the mSloαsubunits associate with the hβ2 subunits before they traffic to membrane surface; the residues E44D45 (hβ2) is a major binding site for mSloαand hβ2 subunits of BK channels and the residues D16E17 (hβ2) is a candidate as a preinactivation site. Our results also demonstrate that the weak binding sites ofαand hβ2 subunits of BK channels exist.
We determine that the hβ2 subunit alone resides in the endoplasmic reticulum (ER), suggesting that trafficking mechanism of hβ2 differs from that of hβ1 opposite to what we predicted previously. We further demonstrate that a four-turnαhelical segment at the N terminus of hβ2 prevents the surface expression of hβ2, that is, the helical segment itself is a retention signal. Using the c-myc epitope tagged the extracellular loop of hβ2, we reveal that the most accessible site by antibody is located at the middle of the extracellular loop, which might provide clues to understand how the auxiliaryβsubunits regulates the toxin sensitivity and the rectification of BK-type channels.
Single large-conductance calcium-activated K+ (BK) channels encoded by mSlo gene usually have a concerted gating, but a Drosophila--dSlo (A2/C2/E2/G5/10) splice variant (dSlo1A)--exhibits very flickery openings. To probe this difference in the gating, we constructed a mutant I323T. This channel exhibits four subconductance levels similar to that of dSlo1A. Rectification of the single channel current-voltage relationship of I323T decreased as [Ca2+]in increased from 10 to 300μM. Mutagenesis suggests that the hydrophobicity of the residue at the position is important for the wild-type gating i.e. increasing hydrophobicity prolongs open duration. Molecular dynamics simulation suggests that four hydrophobic, pore-lining residues at position 323 of mSlo act cooperatively in a“shutter-like”mechanism gating the permeation of K+ ions. We suggest that the appearance of rectification and substates of BK-type channels arise from a reduction of the cooperativity among these four residues and a lower probability of being open.
β2亚基通过其N端的三个疏水性氨基酸FIW产生了失活的BK电流。本文以BK通道β2亚基为研究对象,以HEK293细胞为工具,利用免疫荧光技术,共聚焦显微镜技术,结合分子生物学和电生理学方法,研究了β2亚基的转运机制,探索了其与α亚基的结合位点。主要内容如下:
(1)通过在β2的N端增加三个疏水性的氨基酸FIW(dFIW),我们发现没有记录到预期的失活加强的BK电流,而是记录不到任何电流。通过荧光实验我们发现这种突变体dFIW造成了其本身和共表达的α亚基的ER滞留。通过突变其N端的带电荷的氨基酸D16E17和E44D45,我们发现突变体E44D45能使大部分的α亚基上膜,同时能记录到没有失活的BK电流。我们推断E44D45是结合位点之一。
(2)通过在β2亚基的胞外部分加入抗原决定簇c-myc,利用荧光素耦联的抗体检测发现β2亚基不同于β1亚基,它单独不能被运输到HEK细胞膜上,而是被滞留在内质网(ER)。但与α亚基共表达可以被α亚基带上膜。通过切掉其N端或C端的一些序列我们发现β2亚基N端的一段α螺旋(18-31)造成了其ER滞留。通过在其loop的不同位置加抗原,我们发现K137附近是最容易被抗体接近的区域。
小鼠mslo1形成的BK单通道电流有较长的开放,但线虫dslo(A2/C2/E2/G5/10)在开放时却非常flickery。本文还以BK通道α亚基为研究对象,以非洲爪蟾卵母细胞为工具,利用电生理技术研究BK通道的门控机制。主要内容如下:
我们发现mSlo的突变体I323T会产生跟dslo(A2/C2/E2/G5/10)类似快速开放的单通道电导,并且还有外向整流的性质。而突变dslo(A2/C2/E2/G5/10)相应位置的亲水性氨基酸T337I,发现该通道开放的单通道电导不再flickery。通过单通道电导分析我们发现突变体I323T存在不同亚态的亚电导,这是因为四个亚基之间的协同性被破坏造成的。通过对mSlo的I323位点做一系列的突变,我们发现越疏水性的氨基酸会产生越长的单通道电导。分子动力学模拟表明位于BK通道孔道的四个疏水性氨基酸I323在通道门控过程中起着“开关”作用。因此,我们证明BK通道的亚电导是由于323位置的四个氨基酸残基的协同性降低和开放几率的降低造成的。
Large-conductance voltage- and Ca2+-activated K+ (BK) channels encoded by the msloαandβ2 subunits exist abundantly in rat chromaffin cells, pancreaticβcells and DRG neurons. The extracellular loop of hβ2 acting as the channel regulator influences the rectification and toxin sensitivity of BK channels and the inactivation domain at its N-terminus induces rapid inactivation. However, the regulatory mechanism, especially, the trafficking mechanism of hβ2 is still unknown. With the help of immunofluorescence and patch-clamp techniques, we found that the hβ2 subunit could be completely restrained within the cytoplast of cells by inserting three amino acids FIW at the upstream of its N-terminus termed double FIW or dFIW-hβ2. The dFIW-hβ2 also prevented mSloαsubunit from trafficking onto membrane surface and thus suppressed BK currents to null. Consequently, a novel method has been developed to identify the binding sites between the mSloαand hβ2 subunits of BK channels in this study. Our results reveal that the mSloαsubunits associate with the hβ2 subunits before they traffic to membrane surface; the residues E44D45 (hβ2) is a major binding site for mSloαand hβ2 subunits of BK channels and the residues D16E17 (hβ2) is a candidate as a preinactivation site. Our results also demonstrate that the weak binding sites ofαand hβ2 subunits of BK channels exist.
We determine that the hβ2 subunit alone resides in the endoplasmic reticulum (ER), suggesting that trafficking mechanism of hβ2 differs from that of hβ1 opposite to what we predicted previously. We further demonstrate that a four-turnαhelical segment at the N terminus of hβ2 prevents the surface expression of hβ2, that is, the helical segment itself is a retention signal. Using the c-myc epitope tagged the extracellular loop of hβ2, we reveal that the most accessible site by antibody is located at the middle of the extracellular loop, which might provide clues to understand how the auxiliaryβsubunits regulates the toxin sensitivity and the rectification of BK-type channels.
Single large-conductance calcium-activated K+ (BK) channels encoded by mSlo gene usually have a concerted gating, but a Drosophila--dSlo (A2/C2/E2/G5/10) splice variant (dSlo1A)--exhibits very flickery openings. To probe this difference in the gating, we constructed a mutant I323T. This channel exhibits four subconductance levels similar to that of dSlo1A. Rectification of the single channel current-voltage relationship of I323T decreased as [Ca2+]in increased from 10 to 300μM. Mutagenesis suggests that the hydrophobicity of the residue at the position is important for the wild-type gating i.e. increasing hydrophobicity prolongs open duration. Molecular dynamics simulation suggests that four hydrophobic, pore-lining residues at position 323 of mSlo act cooperatively in a“shutter-like”mechanism gating the permeation of K+ ions. We suggest that the appearance of rectification and substates of BK-type channels arise from a reduction of the cooperativity among these four residues and a lower probability of being open.
引文
[1] Wang, W. , Renal potassium channels: recent developments. Curr Opin Nephrol Hypertens, 2004, 13(5): 549-55
[2] Melman, Y. F. , et al. , KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity. Neuron, 2004, 42(6): 927-37
[3] Korovkina, V. P. and S. K. England, Molecular diversity of vascular potassium channel isoforms. Clin Exp Pharmacol Physiol, 2002, 29(4): 317-23
[4] MacKinnon, R. , R. W. Aldrich, and A. W. Lee, Functional stoichiometry of Shaker potassium channel inactivation. Science, 1993, 262(5134): 757-9
[5] Chung, K. F. , Current and future prospects for drugs to suppress cough. IDrugs, 2003, 6(8): 781-6
[6] Gribkoff, V. K. and R. J. Winquist, Voltage-gated cation channel modulators for the treatment of stroke. Expert Opin Investig Drugs, 2005, 14(5): 579-92
[7] Navarro-Antolin, J. , et al. , Decreased expression of maxi-K+ channel beta1-subunit and altered vasoregulation in hypoxia. Circulation, 2005, 112(9): 1309-15
[8] Melman, A. , et al. , The first human trial for gene transfer therapy for the treatment of erectile dysfunction: preliminary results. Eur Urol, 2005, 48(2): 314-8
[9] Young, R. C. , R. Schumann, and P. Zhang, Intracellular calcium gradients in cultured human uterine smooth muscle: a functionally important subplasmalemmal space. Cell Calcium, 2001, 29(3): 183-9
[10]杨宝峰.离子通道药理学.北京:人民卫生出版社, 2005(ISBN 7-117- 06634- 2/R, 6635)
[11] Kuo, A. , et al. , Crystal structure of the potassium channel KirBac1, 1 in the closed state. Science, 2003, 300(5627): 1922-6
[12] McCleverty, C. J. , et al. , Crystal structure of the human TRPV2 channel ankyrin repeat domain. Protein Sci, 2006, 15(9): 2201-6
[13] Craven, K. B. and W. N. Zagotta, CNG and HCN channels: two peas, one pod. Annu Rev Physiol, 2006, 68: 375-401
[14] Bright, J. N. , et al. , Conformational dynamics of helix S6 from Shaker potassium channel: simulation studies. Biopolymers, 2002, 64(6): 303-13
[15] Zhou, M. , et al. , Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors. Nature, 2001, 411(6838): 657-61
[16] Lopez-Barneo, J. and A. Castellano, Multiple facets of maxi-k+ channels: the heme connection. J Gen Physiol, 2005, 126(1): 1-5
[17] Nehrke, K. , C. C. Quinn, and T. Begenisich, Molecular identification of Ca2+-activated K+ channels in parotid acinar cells. Am J Physiol Cell Physiol, 2003, 284(2): C535-46
[18] Oshiro, T. , et al. , Delayed expression of large conductance K+ channels reshaping agonist-induced currents in mouse pancreatic acinar cells. J Physiol, 2005, 563(Pt 2): 379-91
[19] Nagaya, N. and D. M. Papazian, Potassium channel alpha and beta subunits assemble in the endoplasmic reticulum. J Biol Chem, 1997, 272(5): 3022-7
[20] Makhina, E. N. and C. G. Nichols, Independent trafficking of KATP channel subunits to the plasma membrane. J Biol Chem, 1998, 273(6): 3369-74
[21] Kosolapov, A. and C. Deutsch, Folding of the voltage-gated K+ channel T1 recognition domain. J Biol Chem, 2003, 278(6): 4305-13
[22] Haigh, N. G. and A. E. Johnson, A new role for BiP: closing the aqueous translocon pore during protein integration into the ER membrane. J Cell Biol, 2002, 156(2): 261-70
[23] Menetret, J. F. , et al. , The structure of ribosome-channel complexes engaged in protein translocation. Mol Cell, 2000, 6(5): 1219-32
[24] Deutsch, C. , The birth of a channel. Neuron, 2003, 40(2): 265-76
[25] Lovett, P. S. and E. J. Rogers, Ribosome regulation by the nascent peptide. Microbiol Rev, 1996, 60(2): 366-85
[26] Morris, D. R. and A. P. Geballe, Upstream open reading frames as regulators of mRNA translation. Mol Cell Biol, 2000, 20(23): 8635-42
[27] Ehrenberg, M. and T. Tenson, A new beginning of the end of translation. Nat Struct Biol, 2002, 9(2): 85-7
[28] Anderson, D. J. , P. Walter, and G. Blobel, Signal recognition protein is required for the integration of acetylcholine receptor delta subunit, a transmembrane glycoprotein, into the endoplasmic reticulum membrane. J Cell Biol, 1982, 93(2): 501-6
[29] Chatterjee, K. , et al. , Hypertrophic cardiomyopathy--therapy with slow channel inhibiting agents. Prog Cardiovasc Dis, 1982, 25(3): 193-210
[30] Crowley, K. S. , et al. , Secretory proteins move through the endoplasmic reticulum membrane via an aqueous, gated pore. Cell, 1994, 78(3): 461-71
[31] Liao, S. , et al. , Both lumenal and cytosolic gating of the aqueous ER translocon pore are regulated from inside the ribosome during membrane protein integration. Cell, 1997, 90(1): 31-41
[32] Tu, L. , et al. , Transmembrane biogenesis of Kv1, 3. Biochemistry, 2000, 39(4): 824-36
[33] Fedorov, A. N. and T. O. Baldwin, Contribution of cotranslational folding to the rate of formation of native protein structure. Proc Natl Acad Sci U S A, 1995, 92(4): 1227-31
[34] Makeyev, E. V. , V. A. Kolb, and A. S. Spirin, Enzymatic activity of the ribosome-bound nascent polypeptide. FEBS Lett, 1996, 378(2): 166-70
[35] Schulteis, C. T. , N. Nagaya, and D. M. Papazian, Subunit folding and assembly steps are interspersed during Shaker potassium channel biogenesis. J Biol Chem,1998, 273(40): 26210-7
[36] Sarma, J. D. , F. Wang, and M. Koval, Targeted gap junction protein constructs reveal connexin-specific differences in oligomerization. J Biol Chem, 2002, 277(23): 20911-8
[37] Margeta-Mitrovic, M. , Y. N. Jan, and L. Y. Jan, A trafficking checkpoint controls GABA(B) receptor heterodimerization. Neuron, 2000, 27(1): 97-106
[38] Scott, S. P. , et al. , A functioning chimera of the cyclic nucleotide-binding domain from the bovine retinal rod ion channel and the DNA-binding domain from catabolite gene-activating protein. Biochemistry, 2001, 40(25): 7464-73
[39] Standley, S. , et al. , PDZ domain suppression of an ER retention signal in NMDA receptor NR1 splice variants. Neuron, 2000, 28(3): 887-98
[40] Zerangue, N. , et al. , A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron, 1999, 22(3): 537-48
[41] Wang, J. M. , et al. , A transmembrane motif governs the surface trafficking of nicotinic acetylcholine receptors. Nat Neurosci, 2002, 5(10): 963-70
[42] Ma, D. , et al. , Role of ER export signals in controlling surface potassium channel numbers. Science, 2001, 291(5502): 316-9
[43] Sharma, N. , et al. , The C terminus of SUR1 is required for trafficking of KATP channels. J Biol Chem, 1999, 274(29): 20628-32
[44] Stockklausner, C. , et al. , A sequence motif responsible for ER export and surface expression of Kir2. 0 inward rectifier K(+) channels. FEBS Lett, 2001, 493(2-3): 129-33
[45] Xia, H. , Z. D. Hornby, and R. C. Malenka, An ER retention signal explains differences in surface expression of NMDA and AMPA receptor subunits. Neuropharmacology, 2001, 41(6): 714-23
[46] Tiffany, A. M. , et al. , PSD-95 and SAP97 exhibit distinct mechanisms for regulating K(+) channel surface expression and clustering. J Cell Biol, 2000,148(1): 147-58
[47] Babenko, A. P. , L. Aguilar-Bryan, and J. Bryan, A view of sur/KIR6. X, KATP channels. Annu Rev Physiol, 1998, 60: 667-87
[48] Gilbert, A. , et al. , Delta F508 CFTR localizes in the endoplasmic reticulum-Golgi intermediate compartment in cystic fibrosis cells. Exp Cell Res, 1998, 242(1): 144-52
[49] Trudeau, M. C. and W. N. Zagotta, An intersubunit interaction regulates trafficking of rod cyclic nucleotide-gated channels and is disrupted in an inherited form of blindness. Neuron, 2002, 34(2): 197-207
[50] Shi, X. P. , et al. , The subcellular distribution of eukaryotic translation initiation factor, eIF-5A, in cultured cells. Exp Cell Res, 1996, 225(2): 348-56
[51] Goldstein, S. A. , et al. , Potassium leak channels and the KCNK family of two-P-domain subunits. Nat Rev Neurosci, 2001, 2(3): 175-84
[52] Lesage, F. and M. Lazdunski, Molecular and functional properties of two-pore-domain potassium channels. Am J Physiol Renal Physiol, 2000, 279(5): F793-801
[53] Anderson, M. K. , et al. , Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage. Development, 1999, 126(14): 3131-48
[54] Jing, J. , et al. , Fast inactivation of a brain K+ channel composed of Kv1, 1 and Kvbeta1, 1 subunits modulated by G protein beta gamma subunits. EMBO J, 1999, 18(5): 1245-56
[55] Gray, P. C. , J. D. Scott, and W. A. Catterall, Regulation of ion channels by cAMP-dependent protein kinase and A-kinase anchoring proteins. Curr Opin Neurobiol, 1998, 8(3): 330-4
[56] Davare, M. A. , et al. , The A-kinase anchor protein MAP2B and cAMP-dependent protein kinase are associated with class C L-type calcium channels in neurons. JBiol Chem, 1999, 274(42): 30280-7
[57] Ficker, E. , W. Jarolimek, and A. M. Brown, Molecular determinants of inactivation and dofetilide block in ether a-go-go (EAG) channels and EAG-related K(+) channels. Mol Pharmacol, 2001, 60(6): 1343-8
[58] Kennedy, M. E. , et al. , GIRK4 confers appropriate processing and cell surface localization to G-protein-gated potassium channels. J Biol Chem, 1999, 274(4): 2571-82
[59] Ghatta, S. , et al. , Large-conductance, calcium-activated potassium channels: Structural and functional implications. Pharmacol Ther, 2005
[60] Lu, R. , et al. , MaxiK channel partners: physiological impact. J Physiol, 2006, 570(Pt 1): 65-72
[61] Joiner, W. J. , et al. , Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits. Nat Neurosci, 1998, 1(6): 462-9
[62] Yuan, A. , et al. , SLO-2, a K+ channel with an unusual Cl- dependence. Nat Neurosci, 2000, 3(8): 771-9
[63] Salkoff, L. , et al. , High-conductance potassium channels of the SLO family. Nat Rev Neurosci, 2006, 7(12): 921-31
[64] Bhattacharjee, A. , et al. , Slick (Slo2, 1), a rapidly-gating sodium-activated potassium channel inhibited by ATP. J Neurosci, 2003, 23(37): 11681-91
[65] Knaus, H. G. , et al. , Covalent attachment of charybdotoxin to the beta-subunit of the high conductance Ca(2+)-activated K+ channel. Identification of the site of incorporation and implications for channel topology. J Biol Chem, 1994, 269(37): 23336-41
[66] Knaus, H. G. , et al. , Primary sequence and immunological characterization of beta-subunit of high conductance Ca(2+)-activated K+ channel from smooth muscle. J Biol Chem, 1994, 269(25): 17274-8
[67] Dworetzky, S. I. , et al. , Phenotypic alteration of a human BK (hSlo) channel by hSlobeta subunit coexpression: changes in blocker sensitivity, activation/relaxation and inactivation kinetics, and protein kinase A modulation. J Neurosci, 1996, 16(15): 4543-50
[68] Tseng-Crank, J. , et al. , Cloning, expression, and distribution of a Ca(2+)-activated K+ channel beta-subunit from human brain. Proc Natl Acad Sci U S A, 1996, 93(17): 9200-5
[69] Wallner, M. , P. Meera, and L. Toro, Determinant for beta-subunit regulation in high-conductance voltage-activated and Ca(2+)-sensitive K+ channels: an additional transmembrane region at the N terminus. Proc Natl Acad Sci U S A, 1996, 93(25): 14922-7
[70] Hanner, M. , et al. , The beta subunit of the high-conductance calcium-activated potassium channel contributes to the high-affinity receptor for charybdotoxin. Proc Natl Acad Sci U S A, 1997, 94(7): 2853-8
[71] Brenner, R. , et al. , Vasoregulation by the beta1 subunit of the calcium-activated potassium channel. Nature, 2000, 407(6806): 870-6
[72] Cox, D. H. and R. W. Aldrich, Role of the beta1 subunit in large-conductance Ca(2+)-activated K(+) channel gating energetics. Mechanisms of enhanced Ca(2+) sensitivity, in J Gen Physiol, 2000: 411-32
[73] Li, Z. W. , et al. , RINm5f cells express inactivating BK channels whereas HIT cells express noninactivating BK channels. J Neurophysiol, 1999, 81(2): 611-24
[74] Wanner, S. G. , et al. , High-conductance calcium-activated potassium channels in rat brain: pharmacology, distribution, and subunit composition. Biochemistry, 1999, 38(17): 5392-400
[75] Xia, X. M. , J. P. Ding, and C. J. Lingle, Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells. J Neurosci, 1999, 19(13): 5255-64
[76] Uebele, V. N. , et al. , Cloning and functional expression of two families of beta-subunits of the large conductance calcium-activated K+ channel. J Biol Chem, 2000, 275(30): 23211-8
[77] Behrens, R. , et al. , hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large-conductance calcium-activated potassium channel beta subunit family. FEBS Lett, 2000, 474(1): 99-106
[78] Zeng, X. H. , et al. , BK channels with beta3a subunits generate use-dependent slow afterhyperpolarizing currents by an inactivation-coupled mechanism. J Neurosci, 2007, 27(17): 4707-15
[79] Meera, P. , M. Wallner, and L. Toro, A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin. Proc Natl Acad Sci U S A, 2000, 97(10): 5562-7
[80] Wang, B. , B. S. Rothberg, and R. Brenner, Mechanism of beta4 subunit modulation of BK channels. J Gen Physiol, 2006, 127(4): 449-65
[81] Wang, Z. W. , et al. , SLO-1 potassium channels control quantal content of neurotransmitter release at the C. elegans neuromuscular junction. Neuron, 2001, 32(5): 867-81
[82] Pyott, S. J. , et al. , Cochlear function in mice lacking the BK channel alpha, beta1, or beta4 subunits. J Biol Chem, 2007, 282(5): 3312-24
[83] Orio, P. , et al. , New disguises for an old channel: MaxiK channel beta-subunits. News Physiol Sci, 2002, 17: 156-61
[84] Jaggar, J. H. , et al. , Calcium sparks in smooth muscle. Am J Physiol Cell Physiol, 2000, 278(2): C235-56
[85] Pluger, S. , et al. , Mice with disrupted BK channel beta1 subunit gene feature abnormal Ca(2+) spark/STOC coupling and elevated blood pressure. Circ Res, 2000, 87(11): E53-60
[86] Vergara, C. , et al. , Calcium-activated potassium channels. Curr Opin Neurobiol,1998, 8(3): 321-9
[87] Solaro, C. R. , et al. , Inactivating and noninactivating Ca(2+)- and voltage-dependent K+ current in rat adrenal chromaffin cells. J Neurosci, 1995, 15(9): 6110-23
[88] Fettiplace, R. and P. A. Fuchs, Mechanisms of hair cell tuning. Annu Rev Physiol, 1999, 61: 809-34
[89] Ramanathan, K. , et al. , A molecular mechanism for electrical tuning of cochlear hair cells. Science, 1999, 283(5399): 215-7
[90] Meir, A. , et al. , Ion channels in presynaptic nerve terminals and control of transmitter release. Physiol Rev, 1999, 79(3): 1019-88
[91] Gribkoff, V. K. , J. E. Starrett, Jr. , and S. I. Dworetzky, Maxi-K potassium channels: form, function, and modulation of a class of endogenous regulators of intracellular calcium. Neuroscientist, 2001, 7(2): 166-77
[92] Cantrell, A. R. , T. Scheuer, and W. A. Catterall, Voltage-dependent neuromodulation of Na+ channels by D1-like dopamine receptors in rat hippocampal neurons. J Neurosci, 1999, 19(13): 5301-10
[93] Mochida, S. , et al. , Evidence for a voltage-dependent enhancement of neurotransmitter release mediated via the synaptic protein interaction site of N-type Ca2+ channels. Proc Natl Acad Sci U S A, 1998, 95(24): 14523-8
[94] Petersen, O. H. and Y. Maruyama, Calcium-activated potassium channels and their role in secretion. Nature, 1984, 307(5953): 693-6
[95] Robitaille, R. and M. P. Charlton, Presynaptic calcium signals and transmitter release are modulated by calcium-activated potassium channels. J Neurosci, 1992, 12(1): 297-305
[96] Liu, Y. C. , et al. , Neuroregulation by vasoactive intestinal peptide (VIP) of mucus secretion in ferret trachea: activation of BK(Ca) channels and inhibition of neurotransmitter release. Br J Pharmacol, 1999, 126(1): 147-58
[97] Robitaille, R. , et al. , Functional colocalization of calcium and calcium-gated potassium channels in control of transmitter release. Neuron, 1993, 11(4): 645-55
[98] Marrion, N. V. and S. J. Tavalin, Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons. Nature, 1998, 395(6705): 900-5
[99] Issa, F. , et al. , A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: I. Comparisons with healthy control subjects and neuroleptic-treated/unmedicated pairs analyses. Psychiatry Res, 1994, 52(3): 237-49
[100] Sun, X. P. , L. C. Schlichter, and E. F. Stanley, Single-channel properties of BK-type calcium-activated potassium channels at a cholinergic presynaptic nerve terminal. J Physiol, 1999, 518 (3): 639-51
[101] Kang, J. , J. R. Huguenard, and D. A. Prince, Voltage-gated potassium channels activated during action potentials in layer V neocortical pyramidal neurons. J Neurophysiol, 2000, 83(1): 70-80
[102] Prakriya, M. and C. J. Lingle, BK channel activation by brief depolarizations requires Ca2+ influx through L- and Q-type Ca2+ channels in rat chromaffin cells. J Neurophysiol, 1999, 81(5): 2267-78
[103] Neher, E. and B. Sakmann, Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature, 1976, 260(5554): 799-802
[104] Margrie, T. W. , et al. , Targeted whole-cell recordings in the mammalian brain in vivo. Neuron, 2003, 39(6): 911-8
[105] Chalfie, M. , et al. , Green fluorescent protein as a marker for gene expression. Science, 1994, 263(5148): 802-5
[106] Ryan, T. A. , Fluorescent proteins with ties that bind. Nat Biotechnol, 2003, 21(12): 1447-8
[107] Matz, M. V. , et al. , Fluorescent proteins from nonbioluminescent Anthozoaspecies. Nat Biotechnol, 1999, 17(10): 969-73
[108] Jakobs, S. , et al. , EFGP and DsRed expressing cultures of Escherichia coli imaged by confocal, two-photon and fluorescence lifetime microscopy. FEBS Lett, 2000, 479(3): 131-5
[109] Campbell, R. E. , et al. , A monomeric red fluorescent protein. Proc Natl Acad Sci U S A, 2002, 99(12): 7877-82
[110] Shaner, N. C. , et al. , Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat Biotechnol, 2004, 22(12): 1567-72
[111] Gicquiaux, H. , et al. , Rapid internalization and recycling of the human neuropeptide Y Y(1) receptor. J Biol Chem, 2002, 277(8): 6645-55
[112] Zunkler, B. J. , et al. , Mechanism of terfenadine block of ATP-sensitive K(+) channels. Br J Pharmacol, 2000, 130(7): 1571-4
[113] Lang, T. , et al. , Ca2+-triggered peptide secretion in single cells imaged with green fluorescent protein and evanescent-wave microscopy. Neuron, 1997, 18(6): 857-63
[114] Ding, J. P. , Z. W. Li, and C. J. Lingle, Inactivating BK channels in rat chromaffin cells may arise from heteromultimeric assembly of distinct inactivation-competent and noninactivating subunits. Biophys J, 1998, 74(1): 268-89
[115] Li, W. , et al. , Characterization of voltage-and Ca(2+)-activated K(+) channels in rat dorsal root ganglion neurons. J Cell Physiol, 2007, 212(2): 348-357
[116] Orio, P. and R. Latorre, Differential effects of beta 1 and beta 2 subunits on BK channel activity. J Gen Physiol, 2005, 125(4): 395-411
[117] Demo, S. D. and G. Yellen, The inactivation gate of the Shaker K+ channel behaves like an open-channel blocker. Neuron, 1991, 7(5): 743-53
[118] Gomez-Lagunas, F. and C. M. Armstrong, Inactivation in ShakerB K+ channels: a test for the number of inactivating particles on each channel. Biophys J, 1995,68(1): 89-95
[119] Xia, X. M. , J. P. Ding, and C. J. Lingle, Inactivation of BK channels by the NH2 terminus of the beta2 auxiliary subunit: an essential role of a terminal peptide segment of three hydrophobic residues. J Gen Physiol, 2003, 121(2): 125-48
[120] Zarei, M. M. , et al. , A novel MaxiK splice variant exhibits dominant-negative properties for surface expression. J Biol Chem, 2001, 276(19): 16232-9
[121] Zarei, M. M. , et al. , An endoplasmic reticulum trafficking signal prevents surface expression of a voltage- and Ca2+-activated K+ channel splice variant. Proc Natl Acad Sci U S A, 2004, 101(27): 10072-7
[122]徐长法,王.朱. ,生物化学(第三版).北京:高等教育出版社, 2002
[123] Xia, X. M. , et al. , Rectification and rapid activation at low Ca2+ of Ca2+-activated, voltage-dependent BK currents: consequences of rapid inactivation by a novel beta subunit. J Neurosci, 2000, 20(13): 4890-903
[124] Nimigean, C. M. and K. L. Magleby, The beta subunit increases the Ca2+ sensitivity of large conductance Ca2+-activated potassium channels by retaining the gating in the bursting states. J Gen Physiol, 1999, 113(3): 425-40
[125] Orio, P. , et al. , Structural Determinants for Functional Coupling Between the {beta} and {alpha} Subunits in the Ca2+-activated K+ (BK) Channel. J Gen Physiol, 2006, 127(2): 191-204
[126] Quirk, J. C. and P. H. Reinhart, Identification of a novel tetramerization domain in large conductance K(ca) channels. Neuron, 2001, 32(1): 13-23
[127] Gulbis, J. M. , et al. , Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels. Science, 2000, 289(5476): 123-7
[128] Zeng, X. H. , et al. , Gating properties conferred on BK channels by the beta3b auxiliary subunit in the absence of its NH(2)- and COOH termini. J Gen Physiol, 2001, 117(6): 607-28
[129] Bentrop, D. , et al. , NMR structure of the "ball-and-chain" domain of KCNMB2,the beta 2-subunit of large conductance Ca2+- and voltage-activated potassium channels. J Biol Chem, 2001, 276(45): 42116-21
[130] Zhang, Z. , et al. , A limited access compartment between the pore domain and cytosolic domain of the BK channel. J Neurosci, 2006, 26(46): 11833-43
[131] Zeng, X. H. , X. M. Xia, and C. J. Lingle, Redox-sensitive extracellular gates formed by auxiliary beta subunits of calcium-activated potassium channels. Nat Struct Biol, 2003, 10(6): 448-54
[132] Toro, B. , et al. , KCNMB1 regulates surface expression of a voltage and Ca2+-activated K+ channel via endocytic trafficking signals. Neuroscience, 2006, 142(3): 661-9
[133] Zarei, M. M. , et al. , Endocytic trafficking signals in KCNMB2 regulate surface expression of a large conductance voltage and Ca(2+)-activated K+ channel. Neuroscience, 2007, 147(1): 80-9
[134] Savalli, N. , et al. , Modes of Operation of the BKCa Channel {beta}2 Subunit. J Gen Physiol, 2007, 130(1): 117-31
[135] Kuo, A. , et al. , Increasing the diffraction limit and internal order of a membrane protein crystal by dehydration. J Struct Biol, 2003, 141(2): 97-102
[136] Jiang, Y. , et al. , Crystal structure and mechanism of a calcium-gated potassium channel. Nature, 2002, 417(6888): 515-22
[137] Hanner, M. , et al. , The beta subunit of the high conductance calcium-activated potassium channel. Identification of residues involved in charybdotoxin binding. J Biol Chem, 1998, 273(26): 16289-96
[138] Qian, X. , et al. , Slo1 tail domains, but not the Ca2+ bowl, are required for the beta 1 subunit to increase the apparent Ca2+ sensitivity of BK channels. J Gen Physiol, 2002, 120(6): 829-43
[139] Jin, P. , T. M. Weiger, and I. B. Levitan, Reciprocal modulation between the alpha and beta 4 subunits of hSlo calcium-dependent potassium channels. J Biol Chem,2002, 277(46): 43724-9
[140] Krishnamoorthy, G. , et al. , The NH2 terminus of RCK1 domain regulates Ca2+-dependent BK(Ca) channel gating. J Gen Physiol, 2005, 126(3): 227-41
[141] Moss, B. L. , et al. , Ca2+-dependent gating mechanisms for dSlo, a large- conductance Ca2+-activated K+ (BK) channel. Biophys J, 1999, 76(6): 3099-117
[142] Silberberg, S. D. , et al. , Wanderlust kinetics and variable Ca(2+)-sensitivity of Drosophila, a large conductance Ca(2+)-activated K+ channel, expressed in oocytes. Biophys J, 1996, 70(6): 2640-51
[143] Lagrutta, A. A. , et al. , Aromatic residues affecting permeation and gating in dSlo BK channels. Pflugers Arch, 1998, 435(5): 731-9
[144] Zeng, H. , et al. , Mechanisms of two modulatory actions of the channel-binding protein Slob on the Drosophila Slowpoke calcium-dependent potassium channel. J Gen Physiol, 2006, 128(5): 583-91
[145] Wei, A. , et al. , Calcium sensitivity of BK-type KCa channels determined by a separable domain. Neuron, 1994, 13(3): 671-81
[146] Li, H. , et al. , Interaction sites between the Slo1 pore and the NH2 terminus of the beta2 subunit, probed with a three-residue sensor. J Biol Chem, 2007, 282(24): 17720-8
[147] Schwede, T. , et al. , SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Res, 2003, 31(13): 3381-5
[148] Wang, J. , et al. , Development and testing of a general amber force field. J Comput Chem, 2004, 25(9): 1157-74
[149] Yi, H. , et al. , Interaction simulation of hERG K+ channel with its specific BeKm-1 peptide: insights into the selectivity of molecular recognition. J Proteome Res, 2007, 6(2): 611-20
[150] Doyle, D. A. , et al. , The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science, 1998, 280(5360): 69-77
[151] Grosman, C. , M. Zhou, and A. Auerbach, Mapping the conformational wave of acetylcholine receptor channel gating. Nature, 2000, 403(6771): 773-6
[152] Brelidze, T. I. , X. Niu, and K. L. Magleby, A ring of eight conserved negatively charged amino acids doubles the conductance of BK channels and prevents inward rectification. Proc Natl Acad Sci U S A, 2003, 100(15): 9017-22
[153] Xia, X. M. , X. Zeng, and C. J. Lingle, Multiple regulatory sites in large-conductance calcium-activated potassium channels. Nature, 2002, 418(6900): 880-4
[154] Yang, B. , et al. , Pharmacological activation and inhibition of Slack (Slo2, 2) channels. Neuropharmacology, 2006, 51(4): 896-906
[155] Chapman, M. L. and A. M. VanDongen, K channel subconductance levels result from heteromeric pore conformations. J Gen Physiol, 2005, 126(2): 87-103
[156] Magidovich, E. and O. Yifrach, Conserved gating hinge in ligand- and voltage-dependent K+ channels. Biochemistry, 2004, 43(42): 13242-7
[157] Chapman, M. L. , H. M. VanDongen, and A. M. VanDongen, Activation-dependent subconductance levels in the drk1 K channel suggest a subunit basis for ion permeation and gating. Biophys J, 1997, 72(2): 708-19
[158] Li, W. and R. W. Aldrich, Unique inner pore properties of BK channels revealed by quaternary ammonium block. J Gen Physiol, 2004, 124(1): 43-57
[159] Wilkens, C. M. and R. W. Aldrich, State-independent block of BK channels by an intracellular quaternary ammonium. J Gen Physiol, 2006, 128(3): 347-64
[2] Melman, Y. F. , et al. , KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity. Neuron, 2004, 42(6): 927-37
[3] Korovkina, V. P. and S. K. England, Molecular diversity of vascular potassium channel isoforms. Clin Exp Pharmacol Physiol, 2002, 29(4): 317-23
[4] MacKinnon, R. , R. W. Aldrich, and A. W. Lee, Functional stoichiometry of Shaker potassium channel inactivation. Science, 1993, 262(5134): 757-9
[5] Chung, K. F. , Current and future prospects for drugs to suppress cough. IDrugs, 2003, 6(8): 781-6
[6] Gribkoff, V. K. and R. J. Winquist, Voltage-gated cation channel modulators for the treatment of stroke. Expert Opin Investig Drugs, 2005, 14(5): 579-92
[7] Navarro-Antolin, J. , et al. , Decreased expression of maxi-K+ channel beta1-subunit and altered vasoregulation in hypoxia. Circulation, 2005, 112(9): 1309-15
[8] Melman, A. , et al. , The first human trial for gene transfer therapy for the treatment of erectile dysfunction: preliminary results. Eur Urol, 2005, 48(2): 314-8
[9] Young, R. C. , R. Schumann, and P. Zhang, Intracellular calcium gradients in cultured human uterine smooth muscle: a functionally important subplasmalemmal space. Cell Calcium, 2001, 29(3): 183-9
[10]杨宝峰.离子通道药理学.北京:人民卫生出版社, 2005(ISBN 7-117- 06634- 2/R, 6635)
[11] Kuo, A. , et al. , Crystal structure of the potassium channel KirBac1, 1 in the closed state. Science, 2003, 300(5627): 1922-6
[12] McCleverty, C. J. , et al. , Crystal structure of the human TRPV2 channel ankyrin repeat domain. Protein Sci, 2006, 15(9): 2201-6
[13] Craven, K. B. and W. N. Zagotta, CNG and HCN channels: two peas, one pod. Annu Rev Physiol, 2006, 68: 375-401
[14] Bright, J. N. , et al. , Conformational dynamics of helix S6 from Shaker potassium channel: simulation studies. Biopolymers, 2002, 64(6): 303-13
[15] Zhou, M. , et al. , Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors. Nature, 2001, 411(6838): 657-61
[16] Lopez-Barneo, J. and A. Castellano, Multiple facets of maxi-k+ channels: the heme connection. J Gen Physiol, 2005, 126(1): 1-5
[17] Nehrke, K. , C. C. Quinn, and T. Begenisich, Molecular identification of Ca2+-activated K+ channels in parotid acinar cells. Am J Physiol Cell Physiol, 2003, 284(2): C535-46
[18] Oshiro, T. , et al. , Delayed expression of large conductance K+ channels reshaping agonist-induced currents in mouse pancreatic acinar cells. J Physiol, 2005, 563(Pt 2): 379-91
[19] Nagaya, N. and D. M. Papazian, Potassium channel alpha and beta subunits assemble in the endoplasmic reticulum. J Biol Chem, 1997, 272(5): 3022-7
[20] Makhina, E. N. and C. G. Nichols, Independent trafficking of KATP channel subunits to the plasma membrane. J Biol Chem, 1998, 273(6): 3369-74
[21] Kosolapov, A. and C. Deutsch, Folding of the voltage-gated K+ channel T1 recognition domain. J Biol Chem, 2003, 278(6): 4305-13
[22] Haigh, N. G. and A. E. Johnson, A new role for BiP: closing the aqueous translocon pore during protein integration into the ER membrane. J Cell Biol, 2002, 156(2): 261-70
[23] Menetret, J. F. , et al. , The structure of ribosome-channel complexes engaged in protein translocation. Mol Cell, 2000, 6(5): 1219-32
[24] Deutsch, C. , The birth of a channel. Neuron, 2003, 40(2): 265-76
[25] Lovett, P. S. and E. J. Rogers, Ribosome regulation by the nascent peptide. Microbiol Rev, 1996, 60(2): 366-85
[26] Morris, D. R. and A. P. Geballe, Upstream open reading frames as regulators of mRNA translation. Mol Cell Biol, 2000, 20(23): 8635-42
[27] Ehrenberg, M. and T. Tenson, A new beginning of the end of translation. Nat Struct Biol, 2002, 9(2): 85-7
[28] Anderson, D. J. , P. Walter, and G. Blobel, Signal recognition protein is required for the integration of acetylcholine receptor delta subunit, a transmembrane glycoprotein, into the endoplasmic reticulum membrane. J Cell Biol, 1982, 93(2): 501-6
[29] Chatterjee, K. , et al. , Hypertrophic cardiomyopathy--therapy with slow channel inhibiting agents. Prog Cardiovasc Dis, 1982, 25(3): 193-210
[30] Crowley, K. S. , et al. , Secretory proteins move through the endoplasmic reticulum membrane via an aqueous, gated pore. Cell, 1994, 78(3): 461-71
[31] Liao, S. , et al. , Both lumenal and cytosolic gating of the aqueous ER translocon pore are regulated from inside the ribosome during membrane protein integration. Cell, 1997, 90(1): 31-41
[32] Tu, L. , et al. , Transmembrane biogenesis of Kv1, 3. Biochemistry, 2000, 39(4): 824-36
[33] Fedorov, A. N. and T. O. Baldwin, Contribution of cotranslational folding to the rate of formation of native protein structure. Proc Natl Acad Sci U S A, 1995, 92(4): 1227-31
[34] Makeyev, E. V. , V. A. Kolb, and A. S. Spirin, Enzymatic activity of the ribosome-bound nascent polypeptide. FEBS Lett, 1996, 378(2): 166-70
[35] Schulteis, C. T. , N. Nagaya, and D. M. Papazian, Subunit folding and assembly steps are interspersed during Shaker potassium channel biogenesis. J Biol Chem,1998, 273(40): 26210-7
[36] Sarma, J. D. , F. Wang, and M. Koval, Targeted gap junction protein constructs reveal connexin-specific differences in oligomerization. J Biol Chem, 2002, 277(23): 20911-8
[37] Margeta-Mitrovic, M. , Y. N. Jan, and L. Y. Jan, A trafficking checkpoint controls GABA(B) receptor heterodimerization. Neuron, 2000, 27(1): 97-106
[38] Scott, S. P. , et al. , A functioning chimera of the cyclic nucleotide-binding domain from the bovine retinal rod ion channel and the DNA-binding domain from catabolite gene-activating protein. Biochemistry, 2001, 40(25): 7464-73
[39] Standley, S. , et al. , PDZ domain suppression of an ER retention signal in NMDA receptor NR1 splice variants. Neuron, 2000, 28(3): 887-98
[40] Zerangue, N. , et al. , A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron, 1999, 22(3): 537-48
[41] Wang, J. M. , et al. , A transmembrane motif governs the surface trafficking of nicotinic acetylcholine receptors. Nat Neurosci, 2002, 5(10): 963-70
[42] Ma, D. , et al. , Role of ER export signals in controlling surface potassium channel numbers. Science, 2001, 291(5502): 316-9
[43] Sharma, N. , et al. , The C terminus of SUR1 is required for trafficking of KATP channels. J Biol Chem, 1999, 274(29): 20628-32
[44] Stockklausner, C. , et al. , A sequence motif responsible for ER export and surface expression of Kir2. 0 inward rectifier K(+) channels. FEBS Lett, 2001, 493(2-3): 129-33
[45] Xia, H. , Z. D. Hornby, and R. C. Malenka, An ER retention signal explains differences in surface expression of NMDA and AMPA receptor subunits. Neuropharmacology, 2001, 41(6): 714-23
[46] Tiffany, A. M. , et al. , PSD-95 and SAP97 exhibit distinct mechanisms for regulating K(+) channel surface expression and clustering. J Cell Biol, 2000,148(1): 147-58
[47] Babenko, A. P. , L. Aguilar-Bryan, and J. Bryan, A view of sur/KIR6. X, KATP channels. Annu Rev Physiol, 1998, 60: 667-87
[48] Gilbert, A. , et al. , Delta F508 CFTR localizes in the endoplasmic reticulum-Golgi intermediate compartment in cystic fibrosis cells. Exp Cell Res, 1998, 242(1): 144-52
[49] Trudeau, M. C. and W. N. Zagotta, An intersubunit interaction regulates trafficking of rod cyclic nucleotide-gated channels and is disrupted in an inherited form of blindness. Neuron, 2002, 34(2): 197-207
[50] Shi, X. P. , et al. , The subcellular distribution of eukaryotic translation initiation factor, eIF-5A, in cultured cells. Exp Cell Res, 1996, 225(2): 348-56
[51] Goldstein, S. A. , et al. , Potassium leak channels and the KCNK family of two-P-domain subunits. Nat Rev Neurosci, 2001, 2(3): 175-84
[52] Lesage, F. and M. Lazdunski, Molecular and functional properties of two-pore-domain potassium channels. Am J Physiol Renal Physiol, 2000, 279(5): F793-801
[53] Anderson, M. K. , et al. , Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage. Development, 1999, 126(14): 3131-48
[54] Jing, J. , et al. , Fast inactivation of a brain K+ channel composed of Kv1, 1 and Kvbeta1, 1 subunits modulated by G protein beta gamma subunits. EMBO J, 1999, 18(5): 1245-56
[55] Gray, P. C. , J. D. Scott, and W. A. Catterall, Regulation of ion channels by cAMP-dependent protein kinase and A-kinase anchoring proteins. Curr Opin Neurobiol, 1998, 8(3): 330-4
[56] Davare, M. A. , et al. , The A-kinase anchor protein MAP2B and cAMP-dependent protein kinase are associated with class C L-type calcium channels in neurons. JBiol Chem, 1999, 274(42): 30280-7
[57] Ficker, E. , W. Jarolimek, and A. M. Brown, Molecular determinants of inactivation and dofetilide block in ether a-go-go (EAG) channels and EAG-related K(+) channels. Mol Pharmacol, 2001, 60(6): 1343-8
[58] Kennedy, M. E. , et al. , GIRK4 confers appropriate processing and cell surface localization to G-protein-gated potassium channels. J Biol Chem, 1999, 274(4): 2571-82
[59] Ghatta, S. , et al. , Large-conductance, calcium-activated potassium channels: Structural and functional implications. Pharmacol Ther, 2005
[60] Lu, R. , et al. , MaxiK channel partners: physiological impact. J Physiol, 2006, 570(Pt 1): 65-72
[61] Joiner, W. J. , et al. , Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits. Nat Neurosci, 1998, 1(6): 462-9
[62] Yuan, A. , et al. , SLO-2, a K+ channel with an unusual Cl- dependence. Nat Neurosci, 2000, 3(8): 771-9
[63] Salkoff, L. , et al. , High-conductance potassium channels of the SLO family. Nat Rev Neurosci, 2006, 7(12): 921-31
[64] Bhattacharjee, A. , et al. , Slick (Slo2, 1), a rapidly-gating sodium-activated potassium channel inhibited by ATP. J Neurosci, 2003, 23(37): 11681-91
[65] Knaus, H. G. , et al. , Covalent attachment of charybdotoxin to the beta-subunit of the high conductance Ca(2+)-activated K+ channel. Identification of the site of incorporation and implications for channel topology. J Biol Chem, 1994, 269(37): 23336-41
[66] Knaus, H. G. , et al. , Primary sequence and immunological characterization of beta-subunit of high conductance Ca(2+)-activated K+ channel from smooth muscle. J Biol Chem, 1994, 269(25): 17274-8
[67] Dworetzky, S. I. , et al. , Phenotypic alteration of a human BK (hSlo) channel by hSlobeta subunit coexpression: changes in blocker sensitivity, activation/relaxation and inactivation kinetics, and protein kinase A modulation. J Neurosci, 1996, 16(15): 4543-50
[68] Tseng-Crank, J. , et al. , Cloning, expression, and distribution of a Ca(2+)-activated K+ channel beta-subunit from human brain. Proc Natl Acad Sci U S A, 1996, 93(17): 9200-5
[69] Wallner, M. , P. Meera, and L. Toro, Determinant for beta-subunit regulation in high-conductance voltage-activated and Ca(2+)-sensitive K+ channels: an additional transmembrane region at the N terminus. Proc Natl Acad Sci U S A, 1996, 93(25): 14922-7
[70] Hanner, M. , et al. , The beta subunit of the high-conductance calcium-activated potassium channel contributes to the high-affinity receptor for charybdotoxin. Proc Natl Acad Sci U S A, 1997, 94(7): 2853-8
[71] Brenner, R. , et al. , Vasoregulation by the beta1 subunit of the calcium-activated potassium channel. Nature, 2000, 407(6806): 870-6
[72] Cox, D. H. and R. W. Aldrich, Role of the beta1 subunit in large-conductance Ca(2+)-activated K(+) channel gating energetics. Mechanisms of enhanced Ca(2+) sensitivity, in J Gen Physiol, 2000: 411-32
[73] Li, Z. W. , et al. , RINm5f cells express inactivating BK channels whereas HIT cells express noninactivating BK channels. J Neurophysiol, 1999, 81(2): 611-24
[74] Wanner, S. G. , et al. , High-conductance calcium-activated potassium channels in rat brain: pharmacology, distribution, and subunit composition. Biochemistry, 1999, 38(17): 5392-400
[75] Xia, X. M. , J. P. Ding, and C. J. Lingle, Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells. J Neurosci, 1999, 19(13): 5255-64
[76] Uebele, V. N. , et al. , Cloning and functional expression of two families of beta-subunits of the large conductance calcium-activated K+ channel. J Biol Chem, 2000, 275(30): 23211-8
[77] Behrens, R. , et al. , hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large-conductance calcium-activated potassium channel beta subunit family. FEBS Lett, 2000, 474(1): 99-106
[78] Zeng, X. H. , et al. , BK channels with beta3a subunits generate use-dependent slow afterhyperpolarizing currents by an inactivation-coupled mechanism. J Neurosci, 2007, 27(17): 4707-15
[79] Meera, P. , M. Wallner, and L. Toro, A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin. Proc Natl Acad Sci U S A, 2000, 97(10): 5562-7
[80] Wang, B. , B. S. Rothberg, and R. Brenner, Mechanism of beta4 subunit modulation of BK channels. J Gen Physiol, 2006, 127(4): 449-65
[81] Wang, Z. W. , et al. , SLO-1 potassium channels control quantal content of neurotransmitter release at the C. elegans neuromuscular junction. Neuron, 2001, 32(5): 867-81
[82] Pyott, S. J. , et al. , Cochlear function in mice lacking the BK channel alpha, beta1, or beta4 subunits. J Biol Chem, 2007, 282(5): 3312-24
[83] Orio, P. , et al. , New disguises for an old channel: MaxiK channel beta-subunits. News Physiol Sci, 2002, 17: 156-61
[84] Jaggar, J. H. , et al. , Calcium sparks in smooth muscle. Am J Physiol Cell Physiol, 2000, 278(2): C235-56
[85] Pluger, S. , et al. , Mice with disrupted BK channel beta1 subunit gene feature abnormal Ca(2+) spark/STOC coupling and elevated blood pressure. Circ Res, 2000, 87(11): E53-60
[86] Vergara, C. , et al. , Calcium-activated potassium channels. Curr Opin Neurobiol,1998, 8(3): 321-9
[87] Solaro, C. R. , et al. , Inactivating and noninactivating Ca(2+)- and voltage-dependent K+ current in rat adrenal chromaffin cells. J Neurosci, 1995, 15(9): 6110-23
[88] Fettiplace, R. and P. A. Fuchs, Mechanisms of hair cell tuning. Annu Rev Physiol, 1999, 61: 809-34
[89] Ramanathan, K. , et al. , A molecular mechanism for electrical tuning of cochlear hair cells. Science, 1999, 283(5399): 215-7
[90] Meir, A. , et al. , Ion channels in presynaptic nerve terminals and control of transmitter release. Physiol Rev, 1999, 79(3): 1019-88
[91] Gribkoff, V. K. , J. E. Starrett, Jr. , and S. I. Dworetzky, Maxi-K potassium channels: form, function, and modulation of a class of endogenous regulators of intracellular calcium. Neuroscientist, 2001, 7(2): 166-77
[92] Cantrell, A. R. , T. Scheuer, and W. A. Catterall, Voltage-dependent neuromodulation of Na+ channels by D1-like dopamine receptors in rat hippocampal neurons. J Neurosci, 1999, 19(13): 5301-10
[93] Mochida, S. , et al. , Evidence for a voltage-dependent enhancement of neurotransmitter release mediated via the synaptic protein interaction site of N-type Ca2+ channels. Proc Natl Acad Sci U S A, 1998, 95(24): 14523-8
[94] Petersen, O. H. and Y. Maruyama, Calcium-activated potassium channels and their role in secretion. Nature, 1984, 307(5953): 693-6
[95] Robitaille, R. and M. P. Charlton, Presynaptic calcium signals and transmitter release are modulated by calcium-activated potassium channels. J Neurosci, 1992, 12(1): 297-305
[96] Liu, Y. C. , et al. , Neuroregulation by vasoactive intestinal peptide (VIP) of mucus secretion in ferret trachea: activation of BK(Ca) channels and inhibition of neurotransmitter release. Br J Pharmacol, 1999, 126(1): 147-58
[97] Robitaille, R. , et al. , Functional colocalization of calcium and calcium-gated potassium channels in control of transmitter release. Neuron, 1993, 11(4): 645-55
[98] Marrion, N. V. and S. J. Tavalin, Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons. Nature, 1998, 395(6705): 900-5
[99] Issa, F. , et al. , A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: I. Comparisons with healthy control subjects and neuroleptic-treated/unmedicated pairs analyses. Psychiatry Res, 1994, 52(3): 237-49
[100] Sun, X. P. , L. C. Schlichter, and E. F. Stanley, Single-channel properties of BK-type calcium-activated potassium channels at a cholinergic presynaptic nerve terminal. J Physiol, 1999, 518 (3): 639-51
[101] Kang, J. , J. R. Huguenard, and D. A. Prince, Voltage-gated potassium channels activated during action potentials in layer V neocortical pyramidal neurons. J Neurophysiol, 2000, 83(1): 70-80
[102] Prakriya, M. and C. J. Lingle, BK channel activation by brief depolarizations requires Ca2+ influx through L- and Q-type Ca2+ channels in rat chromaffin cells. J Neurophysiol, 1999, 81(5): 2267-78
[103] Neher, E. and B. Sakmann, Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature, 1976, 260(5554): 799-802
[104] Margrie, T. W. , et al. , Targeted whole-cell recordings in the mammalian brain in vivo. Neuron, 2003, 39(6): 911-8
[105] Chalfie, M. , et al. , Green fluorescent protein as a marker for gene expression. Science, 1994, 263(5148): 802-5
[106] Ryan, T. A. , Fluorescent proteins with ties that bind. Nat Biotechnol, 2003, 21(12): 1447-8
[107] Matz, M. V. , et al. , Fluorescent proteins from nonbioluminescent Anthozoaspecies. Nat Biotechnol, 1999, 17(10): 969-73
[108] Jakobs, S. , et al. , EFGP and DsRed expressing cultures of Escherichia coli imaged by confocal, two-photon and fluorescence lifetime microscopy. FEBS Lett, 2000, 479(3): 131-5
[109] Campbell, R. E. , et al. , A monomeric red fluorescent protein. Proc Natl Acad Sci U S A, 2002, 99(12): 7877-82
[110] Shaner, N. C. , et al. , Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat Biotechnol, 2004, 22(12): 1567-72
[111] Gicquiaux, H. , et al. , Rapid internalization and recycling of the human neuropeptide Y Y(1) receptor. J Biol Chem, 2002, 277(8): 6645-55
[112] Zunkler, B. J. , et al. , Mechanism of terfenadine block of ATP-sensitive K(+) channels. Br J Pharmacol, 2000, 130(7): 1571-4
[113] Lang, T. , et al. , Ca2+-triggered peptide secretion in single cells imaged with green fluorescent protein and evanescent-wave microscopy. Neuron, 1997, 18(6): 857-63
[114] Ding, J. P. , Z. W. Li, and C. J. Lingle, Inactivating BK channels in rat chromaffin cells may arise from heteromultimeric assembly of distinct inactivation-competent and noninactivating subunits. Biophys J, 1998, 74(1): 268-89
[115] Li, W. , et al. , Characterization of voltage-and Ca(2+)-activated K(+) channels in rat dorsal root ganglion neurons. J Cell Physiol, 2007, 212(2): 348-357
[116] Orio, P. and R. Latorre, Differential effects of beta 1 and beta 2 subunits on BK channel activity. J Gen Physiol, 2005, 125(4): 395-411
[117] Demo, S. D. and G. Yellen, The inactivation gate of the Shaker K+ channel behaves like an open-channel blocker. Neuron, 1991, 7(5): 743-53
[118] Gomez-Lagunas, F. and C. M. Armstrong, Inactivation in ShakerB K+ channels: a test for the number of inactivating particles on each channel. Biophys J, 1995,68(1): 89-95
[119] Xia, X. M. , J. P. Ding, and C. J. Lingle, Inactivation of BK channels by the NH2 terminus of the beta2 auxiliary subunit: an essential role of a terminal peptide segment of three hydrophobic residues. J Gen Physiol, 2003, 121(2): 125-48
[120] Zarei, M. M. , et al. , A novel MaxiK splice variant exhibits dominant-negative properties for surface expression. J Biol Chem, 2001, 276(19): 16232-9
[121] Zarei, M. M. , et al. , An endoplasmic reticulum trafficking signal prevents surface expression of a voltage- and Ca2+-activated K+ channel splice variant. Proc Natl Acad Sci U S A, 2004, 101(27): 10072-7
[122]徐长法,王.朱. ,生物化学(第三版).北京:高等教育出版社, 2002
[123] Xia, X. M. , et al. , Rectification and rapid activation at low Ca2+ of Ca2+-activated, voltage-dependent BK currents: consequences of rapid inactivation by a novel beta subunit. J Neurosci, 2000, 20(13): 4890-903
[124] Nimigean, C. M. and K. L. Magleby, The beta subunit increases the Ca2+ sensitivity of large conductance Ca2+-activated potassium channels by retaining the gating in the bursting states. J Gen Physiol, 1999, 113(3): 425-40
[125] Orio, P. , et al. , Structural Determinants for Functional Coupling Between the {beta} and {alpha} Subunits in the Ca2+-activated K+ (BK) Channel. J Gen Physiol, 2006, 127(2): 191-204
[126] Quirk, J. C. and P. H. Reinhart, Identification of a novel tetramerization domain in large conductance K(ca) channels. Neuron, 2001, 32(1): 13-23
[127] Gulbis, J. M. , et al. , Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels. Science, 2000, 289(5476): 123-7
[128] Zeng, X. H. , et al. , Gating properties conferred on BK channels by the beta3b auxiliary subunit in the absence of its NH(2)- and COOH termini. J Gen Physiol, 2001, 117(6): 607-28
[129] Bentrop, D. , et al. , NMR structure of the "ball-and-chain" domain of KCNMB2,the beta 2-subunit of large conductance Ca2+- and voltage-activated potassium channels. J Biol Chem, 2001, 276(45): 42116-21
[130] Zhang, Z. , et al. , A limited access compartment between the pore domain and cytosolic domain of the BK channel. J Neurosci, 2006, 26(46): 11833-43
[131] Zeng, X. H. , X. M. Xia, and C. J. Lingle, Redox-sensitive extracellular gates formed by auxiliary beta subunits of calcium-activated potassium channels. Nat Struct Biol, 2003, 10(6): 448-54
[132] Toro, B. , et al. , KCNMB1 regulates surface expression of a voltage and Ca2+-activated K+ channel via endocytic trafficking signals. Neuroscience, 2006, 142(3): 661-9
[133] Zarei, M. M. , et al. , Endocytic trafficking signals in KCNMB2 regulate surface expression of a large conductance voltage and Ca(2+)-activated K+ channel. Neuroscience, 2007, 147(1): 80-9
[134] Savalli, N. , et al. , Modes of Operation of the BKCa Channel {beta}2 Subunit. J Gen Physiol, 2007, 130(1): 117-31
[135] Kuo, A. , et al. , Increasing the diffraction limit and internal order of a membrane protein crystal by dehydration. J Struct Biol, 2003, 141(2): 97-102
[136] Jiang, Y. , et al. , Crystal structure and mechanism of a calcium-gated potassium channel. Nature, 2002, 417(6888): 515-22
[137] Hanner, M. , et al. , The beta subunit of the high conductance calcium-activated potassium channel. Identification of residues involved in charybdotoxin binding. J Biol Chem, 1998, 273(26): 16289-96
[138] Qian, X. , et al. , Slo1 tail domains, but not the Ca2+ bowl, are required for the beta 1 subunit to increase the apparent Ca2+ sensitivity of BK channels. J Gen Physiol, 2002, 120(6): 829-43
[139] Jin, P. , T. M. Weiger, and I. B. Levitan, Reciprocal modulation between the alpha and beta 4 subunits of hSlo calcium-dependent potassium channels. J Biol Chem,2002, 277(46): 43724-9
[140] Krishnamoorthy, G. , et al. , The NH2 terminus of RCK1 domain regulates Ca2+-dependent BK(Ca) channel gating. J Gen Physiol, 2005, 126(3): 227-41
[141] Moss, B. L. , et al. , Ca2+-dependent gating mechanisms for dSlo, a large- conductance Ca2+-activated K+ (BK) channel. Biophys J, 1999, 76(6): 3099-117
[142] Silberberg, S. D. , et al. , Wanderlust kinetics and variable Ca(2+)-sensitivity of Drosophila, a large conductance Ca(2+)-activated K+ channel, expressed in oocytes. Biophys J, 1996, 70(6): 2640-51
[143] Lagrutta, A. A. , et al. , Aromatic residues affecting permeation and gating in dSlo BK channels. Pflugers Arch, 1998, 435(5): 731-9
[144] Zeng, H. , et al. , Mechanisms of two modulatory actions of the channel-binding protein Slob on the Drosophila Slowpoke calcium-dependent potassium channel. J Gen Physiol, 2006, 128(5): 583-91
[145] Wei, A. , et al. , Calcium sensitivity of BK-type KCa channels determined by a separable domain. Neuron, 1994, 13(3): 671-81
[146] Li, H. , et al. , Interaction sites between the Slo1 pore and the NH2 terminus of the beta2 subunit, probed with a three-residue sensor. J Biol Chem, 2007, 282(24): 17720-8
[147] Schwede, T. , et al. , SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Res, 2003, 31(13): 3381-5
[148] Wang, J. , et al. , Development and testing of a general amber force field. J Comput Chem, 2004, 25(9): 1157-74
[149] Yi, H. , et al. , Interaction simulation of hERG K+ channel with its specific BeKm-1 peptide: insights into the selectivity of molecular recognition. J Proteome Res, 2007, 6(2): 611-20
[150] Doyle, D. A. , et al. , The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science, 1998, 280(5360): 69-77
[151] Grosman, C. , M. Zhou, and A. Auerbach, Mapping the conformational wave of acetylcholine receptor channel gating. Nature, 2000, 403(6771): 773-6
[152] Brelidze, T. I. , X. Niu, and K. L. Magleby, A ring of eight conserved negatively charged amino acids doubles the conductance of BK channels and prevents inward rectification. Proc Natl Acad Sci U S A, 2003, 100(15): 9017-22
[153] Xia, X. M. , X. Zeng, and C. J. Lingle, Multiple regulatory sites in large-conductance calcium-activated potassium channels. Nature, 2002, 418(6900): 880-4
[154] Yang, B. , et al. , Pharmacological activation and inhibition of Slack (Slo2, 2) channels. Neuropharmacology, 2006, 51(4): 896-906
[155] Chapman, M. L. and A. M. VanDongen, K channel subconductance levels result from heteromeric pore conformations. J Gen Physiol, 2005, 126(2): 87-103
[156] Magidovich, E. and O. Yifrach, Conserved gating hinge in ligand- and voltage-dependent K+ channels. Biochemistry, 2004, 43(42): 13242-7
[157] Chapman, M. L. , H. M. VanDongen, and A. M. VanDongen, Activation-dependent subconductance levels in the drk1 K channel suggest a subunit basis for ion permeation and gating. Biophys J, 1997, 72(2): 708-19
[158] Li, W. and R. W. Aldrich, Unique inner pore properties of BK channels revealed by quaternary ammonium block. J Gen Physiol, 2004, 124(1): 43-57
[159] Wilkens, C. M. and R. W. Aldrich, State-independent block of BK channels by an intracellular quaternary ammonium. J Gen Physiol, 2006, 128(3): 347-64
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