BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling

Henrike Berkefeld; Claudia A Sailer; Wolfgang Bildl; Volker Rohde; Jörg-Oliver Thumfart; Silke Eble; Norbert Klugbauer; Ellen Reisinger; Josef Bischofberger; Dominik Oliver; Hans-Günther Knaus; Uwe Schulte; Bernd Fakler

doi:10.1126/science.1132915

BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling

Science. 2006 Oct 27;314(5799):615-20. doi: 10.1126/science.1132915.

Authors

Henrike Berkefeld¹, Claudia A Sailer, Wolfgang Bildl, Volker Rohde, Jörg-Oliver Thumfart, Silke Eble, Norbert Klugbauer, Ellen Reisinger, Josef Bischofberger, Dominik Oliver, Hans-Günther Knaus, Uwe Schulte, Bernd Fakler

Affiliation

¹ Institute of Physiology, University of Freiburg, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany.

PMID: 17068255
DOI: 10.1126/science.1132915

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Brain Chemistry
CHO Cells
Calcium / metabolism*
Calcium Channels, L-Type / drug effects
Calcium Channels, L-Type / isolation & purification
Calcium Channels, L-Type / metabolism*
Calcium Channels, N-Type / drug effects
Calcium Channels, N-Type / isolation & purification
Calcium Channels, N-Type / metabolism*
Calcium Signaling
Chromaffin Cells / drug effects
Chromaffin Cells / metabolism
Cricetinae
Cricetulus
Egtazic Acid / analogs & derivatives
Egtazic Acid / pharmacology
Large-Conductance Calcium-Activated Potassium Channels / drug effects
Large-Conductance Calcium-Activated Potassium Channels / isolation & purification
Large-Conductance Calcium-Activated Potassium Channels / metabolism*
Membrane Potentials / drug effects
Molecular Sequence Data
Patch-Clamp Techniques
Potassium / metabolism*
Rats
Signal Transduction*
Transfection
Xenopus

Substances

Cacna1b protein, rat
Calcium Channels, L-Type
Calcium Channels, N-Type
L-type calcium channel alpha(1C)
Large-Conductance Calcium-Activated Potassium Channels
voltage-dependent calcium channel (P-Q type)
Egtazic Acid
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
Potassium
Calcium