Towards a Unified Theory of Calmodulin Regulation (Calmodulation) of Voltage-Gated Calcium and Sodium Channels.
Towards a Unified Theory of Calmodulin Regulation (Calmodulation) of Voltage-Gated Calcium and Sodium Channels.
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DOI：
10.2174/1874467208666150507110359
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发表时间：
2015
影响因子：
2.7
通讯作者：
Yue DT
中科院分区：
文献类型：
--
作者：
Ben-Johny M;Dick IE;Sang L;Limpitikul WB;Kang PW;Niu J;Banerjee R;Yang W;Babich JS;Issa JB;Lee SR;Namkung H;Li J;Zhang M;Yang PS;Bazzazi H;Adams PJ;Joshi-Mukherjee R;Yue DN;Yue DT
电压门控Na和Ca2+通道代表了两个主要的离子通道家族，其能够实现无数的生物学功能，包括动作电位的产生以及细胞中电和化学信号的耦合。这些离子通道的钙调素调节（钙调）包括具有不同生理意义的重要反馈机制。虽然长期以来一直在寻找，但二十年来对通道家族的共同理解仍然难以捉摸，因为这种调制的功能表现和结构基础往往出现分歧。在这里，我们回顾最近的进展，钙调节的钙离子和钠通道的理解，建议在其监管计划的显着相似性。两个通道家族之间的这种相互关系现在为统一的机制框架铺平了道路，以了解重要的钙调素依赖性反馈，并提供了共同的原则，以接近相关的通道病变疾病。一个激动人心的协同研究时代即将到来。
Voltage-gated Na and Ca2+ channels represent two major ion channel families that enable myriad biological functions including the generation of action potentials and the coupling of electrical and chemical signaling in cells. Calmodulin regulation (calmodulation) of these ion channels comprises a vital feedback mechanism with distinct physiological implications. Though long-sought, a shared understanding of the channel families remained elusive for two decades as the functional manifestations and the structural underpinnings of this modulation often appeared to diverge. Here, we review recent advancements in the understanding of calmodulation of Ca2+ and Na channels that suggest a remarkable similarity in their regulatory scheme. This interrelation between the two channel families now paves the way towards a unified mechanistic framework to understand vital calmodulin-dependent feedback and offers shared principles to approach related channelopathic diseases. An exciting era of synergistic study now looms.