OPEN STATE BLOCK BY FENDILINE OF L-TYPE CA-HEART(+ CHANNELS IN VENTRICULAR MYOCYTES FROM RAT)

The effects of fendiline on L-type Ca++ currents [I-Ca(L)] were invest igated in rat ventricular cardiomyocytes using the patch-clamp techniq ue both in the whole-cell disrupted-patch and in the cell-attached con figuration. For comparison, the effects of verapamil were also investi gated. Both compounds depressed the magnitude of whole cell I-Ca(L), v erapamil being about 15 times more potent than fendiline. Verapamil di d not change the time course of the current, whereas fendiline acceler ated its decay when either Ca++ or Ba++ ions were used as charge carri ers. In the presence of the Ca++ agonist BayK8644 (10 mu M), the poten cy ratio of fendiline/verapamil was inverted. BayK8644 (10 mu M) also reversed the potency ratio of verapamil/fendiline in smooth muscle, wi th respect to changes in tension induced by K+ (48 mM). In single chan nel recordings at 0.1 Hz, in the presence of BayK8644(1 mu M) and usin g Ba++ ions as the charge carrier, fendiline (1 mu M) reduced mean ope n time by 34% and channel availability by 8%; the ensemble average cur rent of Ca++ channels was reduced by 43%. In the same experimental con ditions, verapamil (1 mu M) was ineffective. These results can be expl ained by the assumption that fendiline blocks Ca++ channels preferenti ally in the open state, in contrast to verapamil which blocks preferen tially inactivated Ca++ channels.