Depolarization, exocytosis and amino acid release evoked by hyposmolarity from cortical synaptosomes

External osmolarity reduction (20%) led to labelled glutamate, GABA and taurine release from rat brain cortical synaptosomes. A Cl^-- independent, Na⁺-dependent, La³⁺-sensitive and tetrodotoxin (TTX) reduced depolarization of synaptosomes occurred upon hyposmolarity, suggestive of Na⁺ entry through nonselective cation channels. This depolarization, together with cytosolic Ca²⁺ ([Ca ²⁺]_l) increase, resulted in exocytosis, monitored by FM1-43. The release fraction resulting from these phenomena was estimated, by its decrease, by La³⁺, EGTA-AM and tetanus toxin (TeTX), as 34-44% for glutamate, 21-29% for GABA and 18-22% for taurine. Protein kinase C (PKC) activation by phorbol-12-myristate-13-acetate (PMA) increased the hyposmolarity-elicited exocytosis and this activation increased glutamate (80%), GABA (51%) and taurine (42%) hyposmotic efflux. Inhibition by chelerythrine reduced glutamate, GABA and taurine efflux by 64%, 50% and 24%, respectively. The Na⁺-dependence of amino acid release (glutamate 63%, GABA 46% and taurine 29%) may result from both, prevention of the depolarization- exocytosis efflux, and blockade of the carrier reversal operation. Carrier blockade by DL-threo-β-benzyloxy aspartate (TBOA) and NO-711 resulted in 37% and 28% reduction of glutamate and GABA release, respectively. Contribution of the osmolyte leak pathway to amino acid release, estimated by the influence of Cl^- (NPPB) and tyrosine kinase (AG18) blocker, was up to 55% for taurine, but only 10-18% for GABA, with apparently no contribution for glutamate. The predominant osmolyte-type mechanism of taurine release suggest its function in volume control in nerve endings, while glutamate and GABA respond to events concurrent with hyposmolarity by a neurotransmitter-like release mechanism. The hyposmolarity-induced amino acid efflux from nerve endings may have consequences for neuronal excitability during hyponatremia.