The Journal of Neuroscience, August 13, 2008, 28(33):8238-8245; doi:10.1523/JNEUROSCI.2274-08.2008
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Cellular/Molecular
Repolarizing Responses of BKCa–Cav Complexes Are Distinctly Shaped by Their Cav Subunits
Henrike Berkefeld and
Bernd Fakler
Institute of Physiology, University of Freiburg, 79104 Freiburg, Germany
Correspondence should be addressed to Bernd Fakler, Institute of Physiology, University of Freiburg, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany. Email: bernd.fakler{at}physiologie.uni-freiburg.de
Large-conductance Ca2+- and voltage-activated potassium (BKCa) channels shape the firing pattern in many types of excitable cell through their repolarizing K+ conductance. The onset and duration of the BKCa-mediated currents typically initiated by action potentials (APs) appear to be cell-type specific and were shown to vary between 1 ms and up to a few tens of milliseconds. In recent work, we showed that reliable activation of BKCa channels under cellular conditions is enabled by their integration into complexes with voltage-activated Ca2+ (Cav) channels that provide Ca2+ ions at concentrations sufficiently high (
10 µM) for activation of BKCa in the physiological voltage range. Formation of BKCa–Cav complexes is restricted to a subset of Cav channels, Cav1.2 (L-type) and Cav2.1/2.2 (P/Q- and N-type), which differ greatly in their expression pattern and gating properties. Here, we reconstituted distinct BKCa–Cav complexes in Xenopus oocytes and culture cells and used patch-clamp recordings to compare the functional properties of BKCa–Cav1.2 and BKCa–Cav2.1 complexes. Under steady-state conditions, K+ currents mediated by BKCa–Cav2.1 complexes exhibit a considerably faster rise time and reach maximum at potentials markedly more negative than complexes formed by BKCa and Cav1.2, in line with the distinct steady-state activation and gating kinetics of the two Cav subtypes. When AP waveforms were used as a voltage command, K+ currents mediated by BKCa–Cav2.1 occurred at shorter APs and lasted longer than that of BKCa–Cav1.2. These results demonstrate that the repolarizing K+ currents through BKCa–Cav complexes are shaped by the respective Cav subunit and that the distinct Cav channels may adapt BKCa currents to the particular requirements of distinct types of cell.
Key words: Ca2+-activated K+ channels; Cav channels; BKCa channels; calcium signaling; action potential; potassium channel
Received July 9, 2008;
revised June 25, 2008;
accepted July 1, 2008.
Correspondence should be addressed to Bernd Fakler, Institute of Physiology, University of Freiburg, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany. Email: bernd.fakler{at}physiologie.uni-freiburg.de
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