Selective phenylalkylamine block of I(Kr) over other K(+) currents in guinea-pig ventricular myocytes.

Previous studies on verapamil and D600 have established that the Ca(2+)-channel blockers also inhibit delayed-rectifier K(+) currents in cardiac tissues and myocytes. However, estimated IC(50) values range over two to three orders of concentration, and it is unclear whether this reflects a high selectivity by one or both of the phenylalkylamines for particular K(+) channels. The purpose of the present study was to determine the concentration-dependent actions of verapamil and D600 on three defined cardiac K(+) currents. Guinea-pig ventricular myocytes in the conventional whole-cell configuration were bathed with normal Tyrode's or K(+)-free solution, and pulsed from -80 mV for measurement of the effects of 0.01 microM to 3 mM verapamil and D600 on the inwardly-rectifying K(+) current (I:(Kl)) and the two delayed-rectifier K(+) currents, rapidly-activating I:(Kr) and slowly-activating I:(Ks). The phenylalkylamines inhibited both inward- and outward-directed I:(Kl). The IC(50) values for outward I:(Kl) were approximately 220 microM. Verapamil and D600 were approximately equipotent inhibitors of the delayed-rectifier K(+) currents. They inhibited I:(Kr) with IC(50) near 3 microM, and I:(Ks) with IC(50) > or =280 microM. These results are discussed in relation to previous findings on K(+) currents and to the clinical actions of the drugs.