Characterization of the presynaptic calcium channels involved in glutamate exocytosis from rat hippocampal mossy fiber synaptosomes.

Calcium antagonists inhibit both the Ca2(+)-dependent and -independent release of endogenous glutamate from intact synaptosomes. In the present study, the inhibitory potency of several different classes of calcium antagonists were determined under conditions that control for an effect of these compounds on the Ca2(+)-independent component of glutamate release. The following order of inhibitory potency was derived: flunarizine and cinnarizine greater than diltiazem greater than verapamil, nifedipine and nimodipine greater than omega-conotoxin much greater than amiloride, phenytoin, gadolinium and nickel. Only the diphenylpiperazine derivatives inhibited Ca2(+)-dependent glutamate release with an IC50 value of less than 10(-5) M. This finding indicates that no one type of presynaptic calcium channel predominantly mediates Ca2(+)-dependent glutamate release from hippocampal mossy fiber terminals. It is suggested that the exocytosis of glutamate from rat hippocampal mossy fiber synaptosomes may be mediated by multiple types of calcium channels.