ELECTROGENIC UPTAKE OF SULFUR-CONTAINING ANALOGS OF GLUTAMATE AND ASPARTATE BY MULLER CELLS FROM THE SALAMANDER RETINA

1. The effect of sulphur-containing analogues of glutamate and aspartate on the membrane current of glial cells was studied by whole-cell clamping Muller cells isolated from the salamander retina. 2. L-Cysteic acid (CA), L-cysteinesulphinic acid (CSA), L-homocysteic acid (HCA), L-homocysteinesulphinic acid (HCSA) and S-sulpho-L-cysteine (SC) all evoked an inward membrane current that was large at negative potentials, and was smaller (but did not reverse) at more positive potentials up to +30 mV. 3. Removal of external sodium ions abolished the amino acid-evoked currents. Whole-cell clamping with pipettes containing no potassium led to a rapid suppression of the currents, that did not occur when potassium was included in the pipette. 4. The dependence of the currents on sulphur-containing amino acid concentration obeyed first-order Michaelis-Menten kinetics. The current evoked by co-application of L-glutamate and a sulphur-containing analogue was smaller than the sum of the currents produced by glutamate alone and by the sulphur analogue alone. 5. These data are consistent with the sulphur amino acid-evoked current being caused by uptake on the electrogenic glutamate uptake carrier, which co-transports an excess of Na+ ions into the cell, and counter-transports one K+ ion out of the cell. 6. The apparent K(m) (Michaelis-Menten constant) values for activation of uptake by CA (6-mu-M) and by CSA (60-mu-M) are low enough for uptake on the glutamate uptake carrier to be a plausible mechanism for terminating the postulated neurotransmitter action of these agents. However, the apparent K(m) values for uptake of HCA (2.95 mM), HCSA (1.65 mM) and SC (> 1 mM) are much higher than the EC50 (half-maximal effective concentration) concentrations for these agents' activation of NMDA (N-methyl-D-aspartate) channels. 7. Comparing the concentrations of sulphur amino acids needed to activate NMDA channels with their rate of uptake suggests that their potency for causing excitotoxic damage should follow the sequence HCA > SC > HCSA > Glu > CSA > Asp > CA.