Department of Physiology and Membrane Biology, University of California Davis School of Medicine, Davis, CA 95616, USA.
Int J Mol Sci. 2022 Feb 10;23(4):1953. doi: 10.3390/ijms23041953.
The concerted function of the large number of ion channels expressed in excitable cells, including brain neurons, shapes diverse signaling events by controlling the electrical properties of membranes. It has long been recognized that specific groups of ion channels are functionally coupled in mediating ionic fluxes that impact membrane potential, and that these changes in membrane potential impact ion channel gating. Recent studies have identified distinct sets of ion channels that can also physically and functionally associate to regulate the function of either ion channel partner beyond that afforded by changes in membrane potential alone. Here, we review canonical examples of such ion channel partnerships, in which a Ca channel is partnered with a Ca-activated K channel to provide a dedicated route for efficient coupling of Ca influx to K channel activation. We also highlight examples of non-canonical ion channel partnerships between Ca channels and voltage-gated K channels that are not intrinsically Ca sensitive, but whose partnership nonetheless yields enhanced regulation of one or the other ion channel partner. We also discuss how these ion channel partnerships can be shaped by the subcellular compartments in which they are found and provide perspectives on how recent advances in techniques to identify proteins in close proximity to one another in native cells may lead to an expanded knowledge of other ion channel partnerships.
大量离子通道在可兴奋细胞（包括脑神经元）中的协同作用通过控制膜的电学性质来塑造各种信号事件。长期以来，人们一直认为特定的离子通道组在介导影响膜电位的离子流方面是功能偶联的，而这些膜电位的变化会影响离子通道的门控。最近的研究已经确定了不同的离子通道组，它们也可以通过物理和功能上的关联来调节离子通道伙伴的功能，超出了仅仅通过膜电位变化所能提供的功能。在这里，我们回顾了这种离子通道伙伴关系的典型例子，其中钙通道与钙激活的钾通道配对，为钙流入与钾通道激活的有效偶联提供了专门途径。我们还强调了钙通道和电压门控钾通道之间非典型的离子通道伙伴关系的例子，这些例子本身并不具有内在的钙敏感性，但它们的伙伴关系仍然增强了对一个或另一个离子通道伙伴的调节。我们还讨论了这些离子通道伙伴关系如何受到它们所在的亚细胞区室的影响，并探讨了最近在识别天然细胞中彼此靠近的蛋白质的技术方面的进展如何可能导致对其他离子通道伙伴关系的知识扩展。
