Abstract
The aim of the present study was to identify and characterize the receptors and ionic channels mediating the compound response of tectal neurons to exogenous L-glutamate (Glu). Particular attention was paid to the question of whether separate receptors and channels exist for quisqualate (QA) and kainate (KA) and, if so, whether binding to one of these receptors would modify the response elicited through the other. Neurons were dissociated from the superficial gray layer of the superior colliculus from E21 or P1 rats. Between days 14 and 21 in vitro, responsiveness of tectal neurons to Glu and related substances was tested by recording the whole-cell currents induced by rapid superfusion with drug-containing salt solutions. Our experiments showed that tectal neurons express at least 3 distinct types of receptors for acidic amino acids. KA-activated currents (I(KA)) differ from QA- activated currents (I(QA)) in their dose-response characteristics, desensitization patterns, selective blockade with kynurenic acid and suppression by elevated [Ca2+]o, I(KA), but not I(QA), is significantly reduced by low levels of [Cl-]o, and the [Cl-]o-dependent shift of the reversal potential for I(KA) suggests that KA promotes a conductance decrease for Cl-. Such an effect has been ascribed to APB-receptors, but L-2-amino-4-phosphonobutyrate (APB) itself failed to induce current responses in tectal neurons. KA was without effect when administered together, and in equimolar concentrations, with QA. The block of I(KA) was, however, surmounted by applying KA at considerably higher concentrations. It is concluded that QA acts as a low-affinity competitive antagonist at the KA site and as a high-affinity agonist at its own receptor. The response to the endogenous ligand Glu reflects properties of all receptors. QA and KA receptors account for 20–30% (QA) and 49–82% (KA) of the compound current elicited with 100 microM Glu. These results indicate that binding of Glu does not, in contrast to QA, produce any significant suppression of the KA-receptor-mediated current component.