Isacoff E Y, Jan Y N, Jan L Y
Howard Hughes Medical Institute, University of California, San Francisco 94143.
EXS. 1993;63:338-51. doi: 10.1007/978-3-0348-7265-2_18.
The gating of many K+, Na+ and Ca++ channels is driven by changes in membrane potential. Part of the gating mechanism, the voltage sensing S4, a proposed transmembrane segment, has been identified. Movement in the membrane electric field of the charged S4 is thought to precede the opening and closing of the activation gate. The physical basis of the conformational changes involved in gating has yet to be elucidated. Here, we discuss a domain that appears to lie at the cytoplasmic mouth of K+ channels and to form a receptor for the inactivation gate. We examine the possibility that a) the physical attachment of this receptor/mouth to the S4 allows inactivation to be coupled to the voltage dependent conformational changes that open the channel and b) explains the immobilization of gating charge by inactivation. We also address the physiological ramifications of such structural coupling.
许多钾离子、钠离子和钙离子通道的门控是由膜电位的变化驱动的。门控机制的一部分，即电压传感S4（一种推测的跨膜片段）已被确定。带电荷的S4在膜电场中的移动被认为先于激活门的打开和关闭。门控过程中涉及的构象变化的物理基础尚未阐明。在这里，我们讨论一个似乎位于钾离子通道胞质口处并形成失活门受体的结构域。我们研究了以下可能性：a）该受体/通道口与S4的物理连接使失活与打开通道的电压依赖性构象变化相耦合；b）解释了失活导致门控电荷固定的原因。我们还探讨了这种结构耦合的生理后果。
