MODULATION OF EXTRACELLULAR GABA LEVELS IN THE RETINA BY ACTIVATION OF GLIAL P2X-PURINOCEPTORS

1 In the rat retina, gamma-aminobutyric acid (GABA) released as a tran smitter is inactivated by uptake mainly into glial cells (Muller cells ). Activation of P2-purinoceptors in Muller cells increases [Ca2+](i) and the present study was undertaken to see whether this action affect ed the glial release of [H-3]-GABA from the superfused rat isolated re tina. 2 Adenosine 5'-triphosphate (ATP) and the P2X-purinoceptor agoni sts, alpha,beta-methylene-ATP (alpha,beta-meATP) and beta,gamma-methyl eneATP (beta,gamma-meATP) significantly increased the KCl-evoked relea se of [H-3]GABA from the retina. 3 Adenosine and the P2Y-purinoceptor agonist, 2-chloroATP, had no effect on the KCl-evoked release of [H-3] -GABA from the retina. However, 2-methylthioATP (2-Me-S-ATP) significa ntly enhanced the evoked release of [H-3]-GABA. 4 The effect of ATP on the glial release of [H-3]-GABA was abolished by the P2-antagonist, p yridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). 5 When t he superfused retina was exposed to the GABA uptake inhibitor, SKF8997 6A, the enhancing effect of alpha,beta-meATP on the KCl-evoked release of GABA was abolished. 6 The KCl-evoked release of [H-3]-GABA from th e frog retina and rat cerebrocortical slices, which take up GABA mainl y into neurones, was not affected by ATP or alpha,beta-meATP. 7 We con cluded that the glial Muller cells in the rat retina possess P2-recept ors, activation of which increases the 'release' of preloaded [H-3]-GA BA apparently by reducing uptake. On balance, the results suggest the involvement of P2X-purinoceptors, although we cannot exclude the possi bility that P2Y-purinoceptors may be involved. Our results suggest tha t ATP, as well as being a conventional transmitter in the retina, may be involved in neuronal-glial signalling and modulate the extracellula r concentration of GABA.