Modulation of slow waves by hyperpolarization with potassium channel openers in antral smooth muscle of the guinea-pig stomach

Abstract

Modulation of spontaneous electrical activities (slow waves, pacemaker potentials and follower potentials) in response to hyperpolarization produced by the ATP-sensitive K+ channel openers (KCOs) pinacidil or nicorandil was investigated in smooth muscle tissues of the guinea-pig stomach antrum. With hyperpolarization, the amplitude of slow waves and follower potentials was reduced and that of pacemaker potentials was increased, with a minor modulation of their frequency. The attenuation of slow waves was associated with an inhibition of the 1st component and abolition of the 2nd component. All these actions of KCOs were antagonized by glibenclamide. An increase in the extracellular K+ concentration prevented the KCO-induced hyperpolarization with partial restoration of slow waves, suggesting that the inhibition was produced mainly by a decrease in membrane resistance. Exposure of tissues to KCOs for a long period of time (> 20 min) resulted in the reappearance of slow waves displaying both 1st and 2nd components. The 2nd component of the slow wave, which displayed a slower recovery, was inhibited again by 5-hydroxydecanoic acid, an inhibitor of mitochondrial ATP-sensitive K+ channels. Noradrenaline hyperpolarized the membrane by activating apamin-sensitive K+ channels and increased the amplitude and frequency of slow waves through activation of α1-adrenoceptors, actions different from those of KCOs. Thus, inhibition of slow waves by KCOs may be primarily related to the decrease in amplitude of a passive electrotonic component, possibly due to a reduction of the input resistance. The hyperpolarization shifted the threshold potential for generation of the 2nd component of slow waves to negative levels, presumably due to modulation of mitochondrial functions.