Calcium antagonist effects on low-threshold (T-type) calcium current in rat isolated hippocampal CA1 pyramidal...

In CA1 pyramidal cells freshly isolated from the rat hippocampus, the low-threshold (T-type) Ca++ current was induced by step depolarization to potentials more positive than about -60 mV from a holding potential of -100 mV, and reached a peak in the current-voltage relationship around -30 mV. The activation and inactivation processes of the current were highly potential-dependent, and the latter was fitted by a single exponential function. Organic and inorganic Ca++ antagonists dose dependently blocked T-type Ca++ channel in the order of flunarizine greater than nicardipine greater than D600 greater than diltiazem and La greater than Zn++ greater than Cd++ greater than Ni++ greater than Co++, respectively. The inhibitory effects of flunarizine, nicardipine and D600 were voltage- and use-dependent. It was concluded that rat hippocampal neurons possessed a definite class of T-type Ca++ channel characterized by the current kinetics and the high sensitivity to organic Ca++ antagonists. The pharmacologic nature differed from that in other tissues such as cardiac and smooth muscle cells, peripheral neurons and cultured cells.