Abstract
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.