ATP-sensitive K+ currents in gastric myocytes isolated from guinea-pig

ABSTRACT

ATP-sensitive K+ channels (KATP) were not identified in gastric smooth muscle cells. However, in tension recording of intact gastric circular muscle, lemakalim of KATP channels opener in other tissues suppressed mechanical contractions and this effect was blocked by glibenclamide, a specific inhibitor of KATP channels. The aims of this study were to investigate whether KATP channels exist in gastric smooth muscle of guinea-pig and to know its physiological role. Whole cell K+ currents activated by lemakalim were recorded from freshly isolated cells with a 0.1 mM ATP, 140 mM KCl pipette solutions. Lemakalim (10 muM) increased inward currents of -224 +/- 34 pA (n = 13) at -80 mV of holding potential in bath solution contained 90 mM K+. Bath-applied glibenclamide (10 muM) inhibited the lemakalim-activated inward currents by 91 +/- 6% (n = 5). These lemakalim-activated inward currents were reduced by increased intracellular ATP from 0.1 to 3 mM (-41 +/- 12 pA) (n = 5). The reversal potential of the glibenclamide-sensitive inward currents was -5.2 +/- 2.4 mV (n = 3) in external 90 mM K+ and shifted to -14.8 +/- 3.6 mV (n = 3) in external 60 mM K+, which close to equilibrium potential of K+ (EK). External barium and cesium inhibited the lemakalim-activated inward currents dose-dependently. The half-inhibitory dose (IC50) of barium and cesium were 2.3 muM (n = 5) and 0.38 mM (n = 4), respectively. 10 mM tetraethylammonium (TEA) also inhibited the lemakalim-activated inward currents by 66 +/- 15% (n = 5). Both substance P (SP) (5 muM) and acetylcholine (ACh) (5 muM) inhibited lemakalim-activated inward currents. These results suggest that KATP channels exist in the gastric smooth muscle and its modulation by neurotransmitters may play an important role in regulating gastric motility.