BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling.
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.
Berkefeld
Henrike
H
Institute of Physiology, University of Freiburg, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany.
Sailer
Claudia A
CA
Bildl
Wolfgang
W
Rohde
Volker
V
Thumfart
Jörg-Oliver
JO
Eble
Silke
S
Klugbauer
Norbert
N
Reisinger
Ellen
E
Bischofberger
Josef
J
Oliver
Dominik
D
Knaus
Hans-Günther
HG
Schulte
Uwe
U
Fakler
Bernd
B
D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D020013:Calcium Signaling; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D014981:Xenopus
D002118:Calcium; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D004533:Egtazic Acid; D051036:Large-Conductance Calcium-Activated Potassium Channels; D011188:Potassium; C503279:Cacna1b protein, rat; C419385:L-type calcium channel alpha(1C); C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid