Cromakalim activates the K-ATP and enhances spontaneous transient outward potassium currents in rat saphenous arterial myocytes

Bernard Fioretti, Carlo Trequattrini, Luigi Sforna, Alexander Harper, Luigi Catacuzzeno, Fabio Franciolini

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    Abstract

    Potassium channel openers, e.g. cromakalim are held to relax smooth muscle by hyperpolarizing the cell membrane via activation of ATP-sensitive K+ (K-ATP) channels. A recent report indicates that members of this group dilate cerebral arteries also by enhancing the K-Ca-based spontaneous transient outward currents (STOCs) through the activation of mitochondrial K-ATP channels. We extended the study to rat saphenous arterial myocytes, a model for peripheral resistance vessels, to investigate the effects of cromakalim on K-ATP and STOCs, and the underlaying mechanisms. Smooth muscle myocytes were enzymatically dissociated from the saphenous branch of the femoral artery. Macroscopic currents were recorded from acutely isolated cells using the perforated-patch and whole-cell variants of the patch-clamp technique. Predictably metabolic inhibitors and cromakalim activated a background K+ current blocked by glibenclamide, identified as the K-ATP channel. However, in addition, cromakalim markedly increased the amplitude and frequency of STOCs. The latter action was not sensitive to the specific K-ATP channel blocker glibenclamide, excluding the participation of mitocondrial K-ATP channels in this action. In conclusion, this study suggests that, in addition to the opening of K-ATP channels, the increased STOC activity may have an important role in the vasorelaxing action of cromakalim, but through a mechanism different from that reported on cerebral artery. (C) 2008 Elsevier Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)398-402
    Number of pages5
    JournalPharmacological Research
    Volume57
    Issue number5
    DOIs
    Publication statusPublished - May 2008

    Keywords

    • cromakalim
    • spontaneous transient outward currents
    • K-ATP channel
    • glibenclamide
    • large-conductance Ca2+-sensitive K+ channel
    • SMOOTH-MUSCLE-CELLS
    • PORTAL-VEIN
    • CEREBRAL-ARTERIES
    • CHANNEL OPENERS
    • RABBIT
    • CA2+
    • CONDUCTANCE
    • INHIBITION
    • RELAXATION
    • BRL-34915

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