The potassium current activated by 2-nicotinamidoethyl nitrate (nicorandil) in single ventricular cells of guinea pigs

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Abstract
Membrane currents through potassium channels activated by nicorandil, which has a potent coronary vasodilating action, have been studied in ventricular cells of guinea pigs by using the single pipette whole-cell clamp technique. In the presence of 0.1 mM nicorandil, the duration of the action potential was shortened from 196 to 145 ms. Nicorandil markedly increased outward currents at potentials positive to the resting potential. When the difference in the currents before and after the application of nicorandil were plotted against the membrane potential, the current-voltage relation reversed close to the potassium equilibrium potential. The difference current during depolarizing pulses showed no time-dependent relaxation. These results indicate that the current evoked by nicorandil is carried by K + ions and has voltage-independent kinetics. Power-density spectra obtained in the presence of nicorandil were fitted well by a single Lorentzian curve with a corner frequency of 4.4 Hz. The amplitude of the single-channel unit current was estimated from the relation between the variance and the mean current, and was 0.27±0.1 pA ( n = 7) at – 35 mV. The estimated slope conductance was 4.6±1.7 pS. Nicorandil did not affect Ca 2+ currents. It is concluded that nicorandil activates a small-conductance K + channel without affecting the Ca 2+ channel.