title: Repolarizing responses of BKCa-Cav complexes are distinctly shaped by their Cav subunits.
abstract: Large-conductance Ca(2+)- and voltage-activated potassium (BK(Ca)) 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 1 ms and up to a few tens of milliseconds. In recent work, we showed that reliable activation of BK(Ca) channels under cellular conditions is enabled by their integration into complexes with voltage-activated Ca(2+) (Cav) channels that provide Ca(2+) ions at concentrations sufficiently high (> or =10 microM) for activation of BK(Ca) in the physiological voltage range. Formation of BK(Ca)-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 BK(Ca)-Cav complexes in Xenopus oocytes and culture cells and used patch-clamp recordings to compare the functional properties of BK(Ca)-Cav1.2 and BK(Ca)-Cav2.1 complexes. Under steady-state conditions, K(+) currents mediated by BK(Ca)-Cav2.1 complexes exhibit a considerably faster rise time and reach maximum at potentials markedly more negative than complexes formed by BK(Ca) 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 BK(Ca)-Cav2.1 occurred at shorter APs and lasted longer than that of BK(Ca)-Cav1.2. These results demonstrate that the repolarizing K(+) currents through BK(Ca)-Cav complexes are shaped by the respective Cav subunit and that the distinct Cav channels may adapt BK(Ca) currents to the particular requirements of distinct types of cell.
authors.affiliation: Institute of Physiology, University of Freiburg, 79104 Freiburg, Germany. bernd.fakler@physiologie.uni-freiburg.de
authors.forename: Henrike
authors.initials: H
authors.lastname: Berkefeld
authors.forename: Bernd
authors.initials: B
authors.lastname: Fakler
mesh_terms: D000818:Animals; D016466:CHO Cells; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000502:physiology; D020864:Calcium Channels, N-Type / Q000737:chemistry / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000737:chemistry / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D014981:Xenopus
chemical_list: D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; C503279:Cacna1b protein, rat; C494842:Kcnma1 protein, rat; C419385:L-type calcium channel alpha(1C)