Two states of the L-type Ca2+ channel in PC12 cells: different sensitivity to 1,4-dihydropyridines

A omega-conotoxin-resistant component of high K(+)-induced [Ca2+]i increase in PC12 cells was further divided into two components by the difference in sensitivity to 1,4-dihydropyridines. The initial phase (up to 30s) was several times less sensitive to 1,4-dihydropyridines than the following plateau phase (several minutes). On the other hand, diltiazem blocked both phases with the same potency. Verapamil also was only a little more sensitive to the initial phase. All four 1,4-dihydropyridines tested showed 5-10 times more potent inhibition of (+)-[3H]PN200-110 binding in PC12 cells under the depolarizing (70 mM K+) condition than under the non-depolarizing (5 mM K+) condition. The biphasic blockade of the high K(+)-induced [Ca2+]i rise by 1,4-dihydropyridines appears to reflect their different affinities under depolarizing and non-depolarizing conditions.