Differential effect of a dihydropyridine derivative to Ca2+ entry pathways in neuronal preparations

Nicardipine is one of the 1,4-dihydropyridine derivatives known as blockers for the voltage-dependent Ca2+ channels in muscle cells. The effects of nicardipine on the neuronal functions were studied in several neuronal preparations including clonal rat pheochromocytoma (PC12) cells, rat brain synaptosomes and slices. Nicardipine failed to block the Ca2+-dependent action potentials and the after-spike hyperpolarizations evoked by intracellularly injected current pulses in rat pheochromocytoma cells, while the high K+-stimulated Ca2+ influx and ATP release were dose-dependently inhibited in the same cells. In. rat cerebral synaptosomes and cortical slices, nicardipine showed no blockade on the high K+-stimulated Ca2+ influx and transmitter releases. It was then suggested that the voltage-dependent Ca2+ channels are polymorphic among tissues or even in a single cell from the viewpoint of dihydropyridine susceptibility.