EFFECTS OF SG-75 (NICORANDIL) ON ELECTRICAL-ACTIVITY OF CANINE CARDIAC PURKINJE-FIBERS - POSSIBLE INCREASE IN POTASSIUM CONDUCTANCE

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 225  (1) , 198-205
Abstract
The effects of various concentrations (1-1000 .mu.M) of SG-75 were investigated in action potentials of canine Purkinje fibers wth microelectrodes. In normal fibers stimulated at the standard cycle length of 1500 ms, the drug (1-100 .mu.M) 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 pronouced at lower rates of stimulation and lower external K+ concentrations, but the shortening was unchanged in lower external Na+ concentrations. Depolarizations produced by Ba2+ (0.04 mM) and low K+ (.ltoreq. 1.35 mM) solution were partially reversed by the drug; there were no effects on the high K+ (5.4-24.7 mM)-induced depolarizations. Stretch-induced depolarization was partially recovered in the presence of the drug. SG-75 shortened the duration of the slow response produced by isoproterenol (1 .mu.M) in the presence of 24.7 mM K+, with little change in the maximum rate of rise. Apparently, SG-75 increases membrane K+ conductance in cardiac Purkinje fibers by modifying ix1 and iK1 channels without changing the slow inward currents; evidently, these effects are not mediated by muscarinic receptors. The computed action potentials indicated that this view was reasonable.

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