Pharmacological properties of N-methyl-D-aspartate receptors on ganglion cells of an amphibian retina

1. The pharmacological characteristics of the N-methyl-D-aspartate (NMDA) receptors on amphibian retinal ganglion cells were studied to determine their similarities or differences from NMDA receptors found in mammalian central nervous system (CNS) cells. Cells were tested with a variety of NMDA antagonists acting at sites on the NMDA receptor/ion channel complex. 2. Whole-cell voltage-clamp recordings were obtained from ganglion cells of the larval tiger salamander with a retinal slice preparation. All cells responded with inward currents (V(hold) = -70 mV) when exposed to bath applications of NMDA, kainate (KA), and glutamate (GLU). NMDA currents reversed near 0 mV and showed a negative slope conductance region in the presence of external Mg²⁺. 3. NMDA-evoked inward currents could be blocked by application of 300 μM D-2-amino-7-phosphonoheptanoate (DAP7), 100 μM Zn²⁺, 25 μM 7-chloro- kynurenate (7-cl-KYN), 1 μM MK-801, and 5 mM Mg²⁺. These results indicate that like mammalian NMDA receptors the amphibian NMDA receptor possesses binding sites for NMDA, glycine, zinc, dissociative anesthetics, and Mg²⁺. 4. NMDA responses were evoked in the presence of 1 mM extracellular Mg²⁺ in 100% of cells tested when held at -70 mV. Furthermore, there was a resting conductance at -70 mV and membrane current noise that could be attenuated by the application of NMDA-specific antagonists suggesting a tonic activation of NMDA receptors for cells at the resting potential.