Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes.
Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes.
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纳米结构域信号复合体中钙激活的BK通道和钙通透通道的结构和功能耦合。
DOI：
10.3389/fphys.2021.796540
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发表时间：
2021
影响因子：
4
通讯作者：
Yan J
中科院分区：
文献类型：
--
作者：
Shah KR;Guan X;Yan J
离子通道的生化和功能研究表明，许多这些整体膜蛋白通过与许多其他蛋白质物理结合形成大分子信号复合物。这些大分子信号复合物确保了信号转导的特异性和适当的速率。大电导，Ca2+激活的K+ (BK)通道被膜去极化双重激活，细胞内游离Ca2+ ([Ca2+]i)增加。BK通道的激活导致大量的K+外排，因此，快速的膜复极化和关闭电压依赖性Ca2+渗透通道，以限制[Ca2+]i的进一步增加。因此，BK通道介导的K+信号是膜电位和[Ca2+]i的负反馈调节因子，在许多生理过程和疾病中发挥重要作用。然而，单独由成孔、电压和Ca2+感应α亚基形成的BK通道需要高[Ca2+]i水平才能在生理电压条件下激活通道。因此，大多数天然BK通道被认为与纳米域内（距离几十纳米）的Ca2+可渗透通道共定位，以检测Ca2+可渗透通道开放孔周围的高水平[Ca2+]i。在过去的二十年中，关于BK通道与Ca2+渗透性通道偶联的研究进展，包括最近涉及NMDA受体的报道，展示了离子通道之间纳米结构和功能偶联的示例模型，以实现有效的信号转导和负反馈调节。我们在此回顾我们目前对BK通道与不同Ca2+渗透通道的结构和功能耦合的理解。
Biochemical and functional studies of ion channels have shown that many of these integral membrane proteins form macromolecular signaling complexes by physically associating with many other proteins. These macromolecular signaling complexes ensure specificity and proper rates of signal transduction. The large-conductance, Ca2+-activated K+ (BK) channel is dually activated by membrane depolarization and increases in intracellular free Ca2+ ([Ca2+]i). The activation of BK channels results in a large K+ efflux and, consequently, rapid membrane repolarization and closing of the voltage-dependent Ca2+-permeable channels to limit further increases in [Ca2+]i. Therefore, BK channel-mediated K+ signaling is a negative feedback regulator of both membrane potential and [Ca2+]i and plays important roles in many physiological processes and diseases. However, the BK channel formed by the pore-forming and voltage- and Ca2+-sensing α subunit alone requires high [Ca2+]i levels for channel activation under physiological voltage conditions. Thus, most native BK channels are believed to co-localize with Ca2+-permeable channels within nanodomains (a few tens of nanometers in distance) to detect high levels of [Ca2+]i around the open pores of Ca2+-permeable channels. Over the last two decades, advancement in research on the BK channel’s coupling with Ca2+-permeable channels including recent reports involving NMDA receptors demonstrate exemplary models of nanodomain structural and functional coupling among ion channels for efficient signal transduction and negative feedback regulation. We hereby review our current understanding regarding the structural and functional coupling of BK channels with different Ca2+-permeable channels.
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