Chloride and calcium ions separate L-glutamate receptor populations in synaptic membranes.

Cl-/Ca2+-dependent and Cl-/Ca2+-independent L-[3H]glutamate binding sites in rat brain synaptic membranes showed marked differences in their pharmacological properties. One site resembled L-2-amino-4-phosphonobutyrate (L-APB)-sensitive receptors and the other N-methyl-D-aspartate (NMDA) receptors. Inhibition studies demonstrated that L-aspartate was more potent at Cl-/Ca2+-independent than at Cl-/Ca2+-dependent sites although L-glutamate was of similar potency at both sites; the D-isomers of aspartate, glutamate and alpha-aminoadipate exhibited the opposite trend. Quisqualate and ibotenate showed high and low affinity inhibition components in the presence of Cl- and Ca2+, and only low affinity inhibition at Cl-/Ca2+-independent sites. For a series of alpha-amino-omega-phosphono carboxylic acids (propionate-heptanoate), peaks of inhibitory activity in the presence of Cl- and Ca2+ were shifted to l-carbon shorter homologues than in the absence of these ions. These data indicate that the ionic environment is of critical importance for the activity of different physiological receptor populations in vitro.