Abstract

The objective of this study was to determine the concentration-dependent effects of nisoldipine, a dihydropyridine Ca2+ channel blocker, on K+ currents in guinea-pig ventricular myocytes. Myocytes in the conventional whole-cell configuration were bathed in normal Tyrode's solution or K+-free Tyrode's solution for the measurement of the effects of 0.01-100 microM nisoldipine on rapidly activating delayed-rectifier K+ current (I(Kr)), slowly activating delayed-rectifier K+ current (I(Ks)), inwardly rectifying K+ current (I(K1)), and reference L-type Ca2+ current (I(Ca,L)). Nisoldipine inhibited I(Kr) with an IC(50) of 23 microM, and I(Ks) with an IC(50) of 40 microM. The drug also had weak inhibitory effects on inward- and outward-directed I(K1); the IC(50) determined for outward-directed current was 80 microM. Investigation of nisoldipine action on I(Ks) showed that inhibition occurred in the absence of previous pulsing, and with little change in the time courses of activation and deactivation. However, the drug-induced inhibition was significantly weaker at >or =+30 mV than at +10 mV.5 We estimate that nisoldipine is about 30 times less selective for delayed-rectifier K+ channels than for L-type Ca2+ channels in fully polarised guinea-pig ventricular myocytes, and several orders less selective in partially depolarised myocytes.

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