Dependence of 6¦Â-acetoxy-7¦Á-hydroxyroyleanone block of Kv1.2 channels on C-type inactivation

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• 作者：Yuk-Man Leung ; Kar-Lok Wong ; Chia-Huei Lin ; Chia-Chia Chao ; Chun-Hsiao Chou ; Li-Yun Chang ; Siao-Wei Chen ; Tzu-Hurng Cheng and Yueh-Hsiung Kuo
• 关键词：Voltage ; gated K+ channels ; 6β ; acetoxy ; 7α ; hydroxy ; royleanone ; C ; type inactivation ; Block
• 刊名：Cellular and Molecular Life Sciences (CMLS)
• 出版年：2010
• 出版时间：January, 2010
• 年：2010
• 卷：67
• 期：1
• 页码：147-156
• 全文大小：638.2 KB

文摘

Voltage-gated K+ (Kv) channels exhibit slow or C-type inactivation during continuous depolarization. A selective pharmacological agent targeting C-type inactivation is hitherto lacking. Here, we report that 6β-acetoxy-7α-hydroxyroyleanone (AHR), a diterpenoid compound isolated from Taiwania cryptomerioides, can selectively modify C-type inactivation of Kv1.2 channels. Extracellular, but not intracellular, AHR (50 μM) dramatically accelerated the slow decay of Kv currents and left-shifted the steady-state inactivation curve. AHR blocked Kv currents with an IC₅₀ of 17.7 μM. AHR did not affect the kinetics and voltage-dependence of Kv1.2 channel activation. Channel block by AHR was independent of intracellular K+ concentration. In addition, effect of AHR was much attenuated in a Kv1.2 V370G mutant defective in C-type inactivation. Therefore, block of Kv1.2 channels by AHR did not appear to involve direct occlusion of the outer pore but depended on C-type inactivation. AHR could thus be a probe targeting Kv channel C-type inactivation gate.