Comparison of the effects of BAY K 8644 on cardiac Ca²⁺ current and Ca²⁺ channel gating current

Effects of (-)-BAY K 8644 on Ca²⁺ channel function were studied in guinea pig ventricular myocytes. It was found that the compound has both voltage-dependent stimulatory and inhibitory effects on the Ca²⁺ current (I(Ca)), in agreement with prior studies. The basis for these effects was studied by evaluating the effects of (-)-BAY K 8644 on the Ca²⁺ channel gating current. It was found that the voltage-dependent inhibitory effects of the drug on I(Ca) could be well explained by similar reductions in the amount of gating charge moved. However, the stimulatory effect of (-)-BAY K 8644 on I(Ca) could not be simply correlated with changes in the amount of gating charge moved. Although the drug produced a shift of the charge-voltage relationship to more negative potentials, the drug actually reduced the total amount of movable gating charge. Thus it could be demonstrated that there are membrane potentials where (-)-BAY K 8644 reduced the Ca²⁺ channel gating current while enhancing I(Ca). In addition, the drug was found to slow the decay of the gating current during repolarization. It seems likely that (-)- BAY K 8644 has a dual effect on Ca²⁺ channels: affecting both the voltage dependence of gating charge and the relationship between open probability and charge movement.