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

1 Previous studies on verapamil and D600 have established that the Ca2+-cha nnel blockers also inhibit delayed-rectifier K+ currents in cardiac tissues and myocytes. However, estimated IC50 values range over two to three order s of concentration, and it is unclear whether this reflects a high selectiv ity 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. 2 Guinea-pig ventricular myocytes in the conventional whole-cell configurat ion were bathed with normal Tyrode's or K+-free solution, and pulsed from - 80 mV for measurement of the effects of 0.01 muM 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. 3 The phenylalkylamines inhibited both inward- and outward-directed I-Kl Th e IC50 values for outward I-Kl were approximately 220 muM. 4 Verapamil and D600 were approximately equipotent inhibitors of the delaye d-rectifier K+ currents. They inhibited I-Kr with IC50 near 3 muM, and I-Ks With IC50 greater than or equal to 280 muM. These results are discussed in relation to previous findings on K+ currents and to the clinical actions o f the drugs.