title: BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling.
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.
authors.affiliation: Institute of Physiology, University of Freiburg, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Berkefeld
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Sailer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bildl
authors.forename: Volker
authors.initials: V
authors.lastname: Rohde
authors.forename: Jörg-Oliver
authors.initials: JO
authors.lastname: Thumfart
authors.forename: Silke
authors.initials: S
authors.lastname: Eble
authors.forename: Norbert
authors.initials: N
authors.lastname: Klugbauer
authors.forename: Ellen
authors.initials: E
authors.lastname: Reisinger
authors.forename: Josef
authors.initials: J
authors.lastname: Bischofberger
authors.forename: Dominik
authors.initials: D
authors.lastname: Oliver
authors.forename: Hans-Günther
authors.initials: HG
authors.lastname: Knaus
authors.forename: Uwe
authors.initials: U
authors.lastname: Schulte
authors.forename: Bernd
authors.initials: B
authors.lastname: Fakler
mesh_terms: 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
chemical_list: 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