Avdonin V, Shibata E F, Hoshi T
Department of Physiology and Biophysics, University of Iowa, Iowa City 52242, USA.
J Gen Physiol. 1997 Feb;109(2):169-80. doi: 10.1085/jgp.109.2.169.
Dihydropyridines (DHPs) are well known for their effects on L-typed voltage-dependent Ca2+ channels, However, these drugs also affect other voltage-dependent ion channels, including Shaker K+ channels. We examined the effects of DHPs on the Shaker K+ channels expressed in Xenopus oocytes. Intracellular applications of DHPs quickly and reversibly induced apparent inactivation in the Shaker K+ mutant channels with disrupted N- and C-type inactivation. We found that DHPs interact with the open state of the channel as evidenced by the decreased mean open time. The DHPs effects are voltage-dependent, becoming more effective with hyperpolarization. A model which involves binding of two DHP molecules to the channel is consistent with the results obtained in our experiments.
二氢吡啶类(DHPs)因其对L型电压依赖性Ca2+通道的作用而闻名。然而,这些药物也会影响其他电压依赖性离子通道,包括Shaker K+通道。我们研究了二氢吡啶类对非洲爪蟾卵母细胞中表达的Shaker K+通道的影响。细胞内应用二氢吡啶类可快速且可逆地诱导N型和C型失活被破坏的Shaker K+突变通道出现明显失活。我们发现二氢吡啶类与通道的开放状态相互作用,这可通过平均开放时间的缩短得到证明。二氢吡啶类的作用是电压依赖性的,超极化时作用更有效。一个涉及两个二氢吡啶类分子与通道结合的模型与我们实验中获得的结果一致。