GABA induces norepinephrine exocytosis from hippocampal noradrenergic axonterminals by a dual mechanism involving different voltage-sensitive calcium channels

GABA can evoke norepinephrine (NE) release by activating GABA(A) receptors or GABA transporters on noradrenergic terminals. The heterocarrier-induced release occurs by conventional exocytosis. We here characterized the mechan ism of the GABA(A) receptor-induced release and investigated what type(s) o f voltage-sensitive Ca2+ channels (VSCCs) are involved in the GABA heteroca rrier and GABA(A) receptor-evoked release. The effect of GABA in superfused rat hippocampal synaptosomes prelabeled with [H-3]-NE was partially preven ted by bicuculline or the GABA uptake inhibitor SKF 89976A and abolished by blocking both GABA(A) receptors and GABA transporters. The release elicite d through GABA(A) receptors was Ca2+-dependent, prevented by Cd2+ or by bot ulinum toxin C, and modulated through alpha(2) autoreceptors, The GABA(A) r eceptor-evoked release was insensitive to nifedipine and to omega-conotoxin MVIIC, but was inhibited (similar to 50%) by w-conotoxin GVIA, The heteroc arrier-evoked release, nifedipine-insensitive, was inhibited similar to 30% either by omega-conotoxin GVIA or by omega-conotoxin MVIIC; the combined t oxins produced similar to 60% inhibition, To conclude: a) the releases of N E evoked by activation of GABA(A) receptors and GABA heterocarriers are add itive, although they both occur by conventional exocytosis; b) the heteroca rrier-induced release requires activation of N and P/Q type channels, where as the GABA(A) receptor-induced release only involves channels of the N typ e. (C) 1999 Wiley-Liss, Inc.