Omega-Aga IVA selectively inhibits the calcium-dependent fraction of the evoked release of [3H]GABA from synaptosomes.

Abstract

The effect of omega-Aga IVA, a P-type Ca2+ channel blocker, on the release of the inhibitory neurotransmitter GABA and on the elevation of Cai induced by depolarization was investigated in [3H]GABA and fura-2 preloaded mouse brain synaptosomes, respectively. Two strategies (i.e. 20 mM external K+ and veratridine) that depolarize by different mechanisms the preparation were used. High K+ elevates Cai and induces [3H]GABA release in the absence of external Na+ and in the presence of TTX, conditions that abolish veratridine induced responses. The effect of omega-Aga IVA on the Ca2+ and Na+ dependent fractions of the depolarization evoked release of [3H]GABA were separately investigated in synaptosomes depolarized with high K+ in the absence of external Na+ and with veratridine in the absence of external Ca2+, respectively. The Ca2+ dependent fraction of the evoked release of [3H]GABA and the elevation of Ca2+ induced by high K+ are markedly inhibited (about 50%) in synaptosomes exposed to omega-Aga IVA (300 nM) for 3 min before depolarization, whereas the Na+ dependent, Ca2+ independent carrier mediated release of [3H]GABA induced by veratridine, which is sensitive to verapamil and amiloride, is not modified by omega-Aga IVA. Our results indicate that an omega-Aga IVA sensitive type of Ca2+ channel is highly involved in GABA exocytosis.