Berkefeld Henrike, Sailer Claudia A, Bildl Wolfgang, Rohde Volker, Thumfart Jörg-Oliver, Eble Silke, Klugbauer Norbert, Reisinger Ellen, Bischofberger Josef, Oliver Dominik, Knaus Hans-Günther, Schulte Uwe, Fakler Bernd
Institute of Physiology, University of Freiburg, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany.
Science. 2006 Oct 27;314(5799):615-20. doi: 10.1126/science.1132915.
Large-conductance calcium- and voltage-activated potassium channels (BKCa) are dually activated by membrane depolarization and elevation of cytosolic calcium ions (Ca2+). Under normal cellular conditions, BKCa channel activation requires Ca2+ concentrations that typically occur in close proximity to Ca2+ sources. We show that BKCa channels affinity-purified from rat brain are assembled into macromolecular complexes with the voltage-gated calcium channels Cav1.2 (L-type), Cav2.1 (P/Q-type), and Cav2.2 (N-type). Heterologously expressed BKCa-Cav complexes reconstitute a functional "Ca2+ nanodomain" where Ca2+ influx through the Cav channel activates BKCa in the physiological voltage range with submillisecond kinetics. Complex formation with distinct Cav channels enables BKCa-mediated membrane hyperpolarization that controls neuronal firing pattern and release of hormones and transmitters in the central nervous system.
大电导钙和电压激活钾通道（BKCa）由膜去极化和胞质钙离子（Ca2+）浓度升高双重激活。在正常细胞条件下，BKCa通道激活需要通常在靠近Ca2+来源处出现的Ca2+浓度。我们发现，从大鼠脑亲和纯化的BKCa通道与电压门控钙通道Cav1.2（L型）、Cav2.1（P/Q型）和Cav2.2（N型）组装成大分子复合物。异源表达的BKCa-Cav复合物重构了一个功能性的“Ca2+纳米域”，其中通过Cav通道的Ca2+内流在生理电压范围内以亚毫秒级动力学激活BKCa。与不同Cav通道形成复合物可使BKCa介导的膜超极化，从而控制中枢神经系统中的神经元放电模式以及激素和递质的释放。
