Chloride and calcium ions reveal a pharmacologically distinct population of L-glutamate binding sites in synaptic membranes: correspondence between biochemical and electrophysiological data

The effects of Cl-and Ca2+ on the specific binding of L-glutamate and L-aspartate to synaptic plasma membranes (SPMs) were examined. At a concentration of 2.5 mM, CaClz augmented Lglutamate binding 3.34-fold and modified its pharmacological specificity, whereas L-aspartate binding was unaffected. Kinetic analyses of the inhibition of L-glutamate binding by the a-amino-w-phosphonic acid derivatives of propionic (APP), butyric (APB), and valeric (APV) acids demonstrated that, in the presence of CaC12, these homologues competed for the same L-glutamate binding site with Ki values of 16 PM (APB), 39 PM (APV), and >l mM (APP); the L isomer of APB was 15-fold more potent than the D form (Ki values, 5 and 75 PM, respectively). Hill plots indicated an absence of cooperative interactions. These Ki values are in close agreement with those determined electro-' We would like to thank Professors