Vivas Oscar, Moreno Claudia M, Santana Luis F, Hille Bertil
Department of Physiology and Biophysics, University of Washington, Seattle, United States.
Department of Physiology and Membrane Biology, University of California, Davis, Davis, United States.
Elife. 2017 Jun 30;6:e28029. doi: 10.7554/eLife.28029.
Ca-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and Ca1.3 channels, unique Ca1 channels that activate at low voltages. We found that when BK and Ca1.3 channels were co-expressed in the same cell, BK channels started activating near -50 mV, ~30 mV more negative than for activation of co-expressed BK and high-voltage activated Ca2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of Ca1.3 channels surrounding clusters of BK channels and forming a multi-channel complex both in a heterologous system and in rat hippocampal and sympathetic neurons. We propose that this spatial arrangement allows tight tracking between local BK channel activation and the gating of Ca1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials.
BK通道的钙通道依赖性激活对于钙内流和细胞兴奋性的反馈控制至关重要。在此，我们探讨了BK通道与Ca1.3通道之间的功能和空间相互作用，Ca1.3通道是在低电压下激活的独特钙通道。我们发现，当BK通道和Ca1.3通道在同一细胞中共表达时，BK通道在约-50 mV时开始激活，比共表达的BK通道和高电压激活的Ca2.2通道的激活电位负约30 mV。此外，单分子定位显微镜显示，在异源系统以及大鼠海马和交感神经元中，Ca1.3通道的显著簇围绕着BK通道簇，并形成多通道复合体。我们提出，这种空间排列允许在相当负的膜电位下，局部BK通道激活与Ca1.3通道门控之间进行紧密跟踪，有助于在接近动作电位激发阈值的电压下调节神经元兴奋性。
