Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 33, Pages 8238-8245Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2274-08.2008
Keywords
Ca2+ -activated K+ channels; Cav channels; BKCa channels; calcium signaling; action potential; potassium channel
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Funding
- Deutsche Forschungsgemeinschaft [Fa 332/5-3]
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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 BK(Ca-)mediated currents typically initiated by action potentials (APs) appear to be cell-type specific and were shown to vary between 1ms 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 mu M) 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.
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