Reciprocal regulation of the Ca2+ and H+ sensitivity in the SLO1 BK channel conferred by the RCK1 domain
Reciprocal regulation of the Ca2+ and H+ sensitivity in the SLO1 BK channel conferred by the RCK1 domain
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DOI：
10.1038/nsmb.1398
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发表时间：
2008-04-01
影响因子：
16.8
通讯作者：
Hoshi, Toshinori
中科院分区：
文献类型：
--
作者：
Hou, Shangwei;Xu, Rong;Hoshi, Toshinori
越来越多的证据表明，细胞内 H+ 直接刺激大电导 Ca2+- 和电压激活 K+ (SLO1 BK) 通道，从而在膜兴奋性和细胞代谢之间提供至关重要的联系。在这里，我们报道了位于 K+ (RCK) 1 结构域的细胞内电导调节器中的两个组氨酸残基 His365 和 His394，充当 SLO1 BK 通道的 H+ 传感器。 H+ 激活通道需要组氨酸残基和附近带负电荷的残基之间存在静电相互作用，该残基参与通道的高亲和力 Ca2+ 敏感性。相反，His365 和 His394 也参与通道的 Ca2+ 依赖性激活，一旦质子化就充当 Ca2+ 模拟物。因此，RCK1结构域中的一个共同基序介导H+和Ca2+的刺激作用，并为细胞代谢和膜电兴奋性的双向耦合提供基础。
Increasing evidence suggests that intracellular H+ directly stimulates large-conductance Ca2+- and voltage-activated K+ (SLO1 BK) channels, thus providing a crucial link between membrane excitability and cell metabolism. Here we report that two histidine residues, His365 and His394, located in the intracellular regulator of conductance for K+ (RCK) 1 domain, serve as the H+ sensors of the SLO1 BK channel. Activation of the channel by H+ requires electrostatic interactions between the histidine residues and a nearby negatively charged residue involved in the channel's high-affinity Ca2+ sensitivity. Reciprocally, His365 and His394 also participate in the Ca2+- dependent activation of the channel, functioning as Ca2+ mimetics once they are protonated. Therefore, a common motif in the RCK1 domain mediates the stimulatory effects of both H+ and Ca2+, and provides a basis for the bidirectional coupling of cell metabolism and membrane electrical excitability.