EXCITATORY AMINO-ACID RECEPTORS ON ISOLATED RETINAL GANGLION-CELLS FROM THE GOLDFISH

1. Whole-cell currents activated by the excitatory amino acids L-glutamic acid (glutamate, Glu), L-aspartic acid (Asp), and their analogues N-methyl-D-aspartate (NMDA), kainic acid (KA), quisqualic acid (QA), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were recorded from ganglion cells enzymatically dissociated from goldfish retina and grown in culture. All agonists induced detectable whole-cell responses in the majority of cells cultured from 2 to 72 h. 2. Currents activated by each of the agonists were selective for cations (Na+) over anions (Cl-). The responses to Glu, NMDA, and Asp were each potentiated when 1-mu-M glycine was coapplied. Extracellular Mg2+ blocked completely the response to NMDA plus glycine in cells held at negative potentials, but the block was relieved when cells were more depolarized. 3. Dose-response measurements revealed a rank order of sensitivity to the Glu analogues in the presence of 1-mu-M glycine and zero extracellular Mg2+: QA > AMPA > NMDA > KA. Cells were not responsive to APB (L-2-aminophosphonobutyric acid). 4. Kynurenic acid (Ky) produced a noncompetitive block of the NMDA response in the presence of 1-mu-M glycine with a K(i) of 40-mu-M. Responses to KA, QA, and AMPA were blocked competitively by Ky with K(i)s of 72, 148, and 656-mu-M, respectively. QA and AMPA competitively blocked the response to KA with K(i)s of 114-mu-M and 1 mM, respectively. NMDA single channels had a mainstate slope conductance of 27-30 pS and two subconductance levels of 5 and 24 pS at 13-degrees-C in symmetrical Na+. 5. Whole-cell responses to QA and AMPA were highly correlated, suggesting that QA and AMPA activated the same receptor or class of receptors; whereas, responses to QA and KA were not well correlated, suggesting that these agonists at least in part activated separate receptor populations.