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  • Title: Repolarizing responses of BKCa-Cav complexes are distinctly shaped by their Cav subunits.
    Author: Berkefeld H, Fakler B.
    Journal: J Neurosci; 2008 Aug 13; 28(33):8238-45. PubMed ID: 18701686.
    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.
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