The different mechanisms of action of nicorandil and adenosine triphosphate on potassium channels of circular smooth muscle of the guinea-pig small intestine

Abstract

Nicorandil (10 μmol/l–0.3 mmol/l) and ATP (1 μmol/l–0.1 mmol/l) hyperpolarized the membrane of circular smooth muscle of the guinea-pig small intestine and increased conductance of the membrane probably to K ions as estimated by the effect on the current-voltage relationship. In the presence of a maximally hyperpolarizing concentration of nicorandil (0.1 mmol/l), ATP produced a further hyperpolarization of 5 mV. The ATP-induced but not the nicorandil-induced hyperpolarization required the presence of Ca in the medium, and the ATP-induced hyperpolarization was blocked by apamin treatment (1 nmol/l) or by MnCl₂ (1.3 mmol/l). On the other hand, both hyperpolarization responses were blocked by the local anaesthetics procaine (0.1–1 mmol/l), lidocaine (0.1–1 mmol/l) or cocaine (0.3–1 mmol/l), with different potencies. Field stimulation of smooth muscle of the small intestine produced inhibitory junction potentials (i.j.p.s) and these were inhibited by apamin (10 nmol/l–100 nmol/l). In the presence of ATP, the amplitude of the i.j.p.s was markedly reduced, but in the presence of nicorandil the amplitude was only slightly reduced, consistent with the same increase in ionic conductance and hyperpolarization of the membrane. These results indicate that ATP and nicorandil hyperpolarize the membrane by activating different K-channels, i.e. Ca dependent and Ca insensitive K channels, respectively. As assessed from the effects of local anaesthetics and the membrane properties, the circular muscle may also possess other K channels different from the ATP and nicorandil sensitive K channels.