ROLE OF EXTERNAL AND INTERNAL CALCIUM ON HETEROCARRIER-MEDIATED TRANSMITTER RELEASE

Release-regulating heterocarriers exist on brain nerve endings. We hav e investigated in this study the mechanisms involved in the neurotrans mitter release evoked by GABA heterocarrier activation. GABA increased the basal release of [H-3]acetylcholine and [H-3]-noradrenaline from rat hippocampal synaptosomes and of [H-3]dopamine from striatal synapt osomes. These GABA effects, insensitive to GABA receptor antagonists, were prevented by inhibiting GABA uptake but not by blocking noradrena line, choline, or dopamine transport. Lack of extracellular Ca2+ or ad dition of tetrodotoxin selectively abolished the GABA-evoked release o f [H-3]- noradrenaline, leaving unaffected that of [H-3]acetylcholine or [H-3]dopamine. 1,2-Bis(2-aminophenoxy)-ethane- N, N, N',N'-tetraace tic acid acetoxymethyl ester (BAPTA-AM) or vesamicol attenuated the re lease of [H-3]-acetylcholine elicited by GABA. Reserpine, but not BAPT A-AM, prevented the effect of GABA on [H-3]- dopamine release. Autorec eptor activation inhibited the GABA-evoked release of [H-3]noradrenali ne but not that of [H-3]acetylcholine or [H-3]dopamine. It is conclude d that (a) the release of [H-3] noradrenaline consequent to activation of GABA heterocarriers sited on noradrenergic terminals meets the cri teria of a conventional exocytotic process, (b) the extracellular [Ca2 -]-independent releases of [H-3]acetylcholine and [H-3]dopamine appear to occur from vesicles possibly through involvement of intraterminal Ca2+, and (c) autoreceptor activation only affects heterocarrier-media ted vesicular release linked to entry of extracellular Ca2+.