Effects of Arachidonic Acid on ATP-Sensitive K+ Current in Murine Colonic Smooth Muscle Cells

[摘要] References(38)Cited-By(1)The effects of arachidonic acid (AA) and the mechanism through which it modulates ATP-sensitive K+ (KATP) currents were examined in single smooth muscle cells of murine proximal colon. In the current-clamping mode, AA and glibenclamide induced depolarization of membrane potential. Using 0.1 mM ATP and 140 mM K+ solution in the pipette and 90 mM K+ in the bath solution at a −80 mV of holding potential, pinacidil activated the glibenclamide-sensitive inward current. The potential of these currents was reversed to near the equilibrium potential of K+ by 60 mM K+ in the bath solution. AA inhibited KATP currents in a dose-dependent manner. This inhibition was not changed when 1 mM GDPβS was present in the pipette. Chelerythrine, protein kinase C inhibitor, did not block the AA effects. Superoxide dismutase and metabolic inhibitors (indomethacin and nordihydroguaiacretic acid) of AA did not affect the AA-induced inhibition. Eicosatetraynoic acid, a nonmetabolizable analogue of AA, inhibited the KATP currents. These results suggest that AA-induced inhibition of KATP currents is not mediated by G-protein or protein kinase C activation. The inhibitory action is likely to be a possible mechanism of AA-induced membrane depolarization.

[学科分类] 药理学

[关键词] Colonic smooth muscle;ATP-sensitive K+ current;Arachidonic acid