Ca2+-permeable P2X receptor channels in cultured rat retinal ganglion cells

ATP has been identified as an excitatory neurotransmitter in both the CNS a nd peripheral nervous system; however, little is known about the functional properties of ATP-gated channels in central neurons. Here we used a cultur e preparation of the postnatal rat retina to test the responsiveness of ide ntified retinal ganglion cells (RGCs) and putative amacrines to exogenous A TP and other purinoceptor agonists. Rapidly activating ATP-induced currents (I-ATP) were exclusively generated in a subpopulation (similar to 65%) of RGCs. The latter were identified by Thy1.1 immunostaining, repetitive firin g patterns, and activation of glutamatergic autaptic currents. None of the putative amacrine cells was ATP-sensitive. I-ATP could be induced with ATP, ADP, and alpha,beta-mATP but not with adenosine. It was antagonized by sur amin. The current-voltage relationship of I-ATP showed marked inward rectif ication. Dose-response analysis yielded an EC50 of 14.5 mu M, with a Hill c oefficient of 0.9. Noise analysis of I,, suggested a mean single channel co nductance of 2.3 pS. Retinal P2X purinoceptor channels exhibited a high per meability for Ca2+. P-Ca/P-Cs obtained from reversal potentials of I-ATP un der bi-ionic conditions amounted to 2.2 +/- 0.7. In the majority of cells, the decay of I-ATP was biphasic. The degree of current inactivation during the first 2 sec of agonist application was highly variable. Heterogeneity w as also found with respect to the sensitivity to ADP and alpha,beta-mATP an d the blocking action of suramin, suggesting expression of multiple P2X rec eptor subtypes. Our results indicate that activation of P2X receptor channe ls represents an important pathway for Ca2+ influx in postnatal RGCs.