BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling |
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Authors: | 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 |
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Institution: | Institute of Physiology, University of Freiburg, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany. |
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Abstract: | 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. |
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