VERATRIDINE-INDUCED AND GLUTAMATE-INDUCED RELEASE OF [H-3]-GABA FROM CULTURED CHICK RETINA CELLS - POSSIBLE INVOLVEMENT OF A GAT-1-LIKE SUBTYPE OF GABA TRANSPORTER

Four subtypes of GABA carriers (GAT1-GAT4) that transport GABA in a so dium-dependent manner were identified so far. In this report, the sodi um-dependent release of GABA was investigated in cultured chick retina l cells. Opening of voltage-sensitive sodium channels by veratridine o r activation of non-NMDA glutamate receptors induced the release of GA BA from cultured cells. The release of GABA was calcium-independent, b ut could be completely prevented by the substitution of sodium chlorid e by lithium or choline chloride in the extracellular medium, suggesti ng that GABA release could be triggered by multiple mechanisms that le d to the flux of sodium into these cells. Pharmacological experiments revealed that, while GABA uptake was almost completely inhibited by th e GAT-1 blockers NNC-711 (50 mu M) or nipecotic acid (1 mM), the relea se of this amino acid was inhibited by NNC-711, but not by nipecotic a cid. The incubation with beta-alanine (10 mM), a GAT-2/GAT-3 inhibitor , blocked 50% of GABA uptake but had no effect on the release. Our dat a suggest that sodium-dependent GABA release from cultured chick retin a cells is mediated by a GAT-1 like transporter that shows some, but n ot all, the pharmacological properties of the GAT-1 carrier. (C) 1998 Elsevier Science B.V. All rights reserved.