Effects of nicorandil on the membrane currents of rabbit sino-atrial node cells

The effects of nicorandil (SG-75) (3-500 micrograms/ml) on the membrane potential and currents of the rabbit sino-atrial node were studied using the voltage clamp technique. Low concentrations of nicorandil (3-10 micrograms/ml) increased the action potential duration (APD) and depolarized the maximum diastolic potential (DMP), but higher concentrations had no such effect and even decreased APD and tended to hyperpolarize MDP. Regardless of these effects, nicorandil decreased the heart rate concentration-dependently. On the current systems of the sino-atrial node, 3 micrograms/ml of nicorandil decreased the outward current (ik), but concentrations of over 10 micrograms/ml increased it. The voltage dependency of the steady-state activation of ik was unchanged. Nicorandil did not affect the inward current activated by hyperpolarization (Ih) and the slow inward current (is). These results suggest that the cardiac effects induced by nicorandil must have been produced by selective change in the conductance of ik.