Effects of SG-75 (nicorandil) on electrical activity of canine cardiac Purkinje fibers: possible increase in potassium conductance.
The effects of various concentrations (1-1000 microM) of SG-75 nitrate or nicorandil) were investigated in action potentials of canine Purkinje fibers with microelectrodes. In normal fibers stimulated at the standard cycle length of 1500 msec, the drug (1-100 microM) produced dose-dependent shortening in action potential duration without changes in the resting potential, the maximum rate of rise of phase 0 and the slope of phase 4 depolarization. The drug-induced percentage of shortening in the action potential duration was more pronounced at lower rates of stimulation and lower external K+ concentrations, but the shortening was unchanged in lower external Na+ concentrations. Depolarizations produced by Ba++ (0.04 mM) and low K+ (less than or equal to 1.35 mM) solution were partially reversed by the drug, whereas there were no effects on the high K+ (5.4-24.7 mM)-induced depolarizations. Stretch-induced depolarization was also partially recovered in the presence of the drug. SG-75 shortened the duration of the slow response produced by isoproterenol (1 microM) in the presence of 24.7 mM K+, with little change in the maximum rate of rise. We concluded that SG-75 increases membrane K+ conductance in cardiac Purkinje fibers probably by modifying ix1 and iK1 channels without changing the slow inward currents and that the effects are not mediated by muscarinic receptors. The computed action potentials indicated that this view was reasonable.