L-homocysteic acid selectively activates N-methyl-D-aspartate receptors of rat retinal ganglion cells.

To explore the possible role of L-homocysteic acid (HCA) as a retinal transmitter, whole-cell recordings with patch electrodes were performed on isolated rat retinal ganglion cells (RGCs) in culture. HCA elicited an inward current at -60 mV. Similar to currents evoked at this potential in RGCs by N-methyl-D-aspartate (NMDA), HCA-activated currents were of relatively small amplitude (10-150 pA), and the noise level increased dramatically during the response. When HCA was co-applied with concentrations of NMDA that elicited a maximal response, the current was not increased over that of NMDA alone. HCA-evoked currents were almost completely blocked by the NMDA antagonists D-2-amino-5-phosphonovalerate (D-AP5), Mg2+, or 7-chlorokynurenate (7-Cl KYN). Unlike its effects on other preparations, even millimolar concentrations of HCA did not activate kainate-like currents. These observations suggest that HCA specifically activates the NMDA receptor-channel complex of rat RGCs.