Action of nifedipine or BAY K8644 is dependent on calcium channel state in single smooth muscle cells from rabbit ear artery.

The actions of nifedipine or BAY K 8644 were studied on barium currents recorded from single, collagenase- and elastase-dispersed, smooth muscle cells from the rabbit ear artery using the whole-cell configuration of the patch-clamp technique. Nifedipine (3 microM) caused a reduction in the barium current (IBa) evoked by steps to potentials positive of -10 mV. This was characterized by a pronounced 'initial' block, an increase in the rate of current decay during the voltage-clamp step, but by no increase in block if pulses were repeated every 600 ms. Rapid extracellular application of nifedipine (1 microM) during the sustained current component (using a new concentration-jump technique) was found to have no effect on IBa over 4s at +20 mV, but after returning to the holding potential (-60 mV) for 10s, sustained IBa was subsequently abolished. BAY K 8644 (1 microM) increased IBa at all potentials, and on rapid application during the sustained current component markedly potentiated IBa. The results suggest that nifedipine binds with high affinity to the closed, available state of the Ca++ channels but they do not suggest binding to the open or inactivated states. The effect of BAY K 8644 is consistent with high affinity binding to the open or inactivated and to the closed, available states.