RECEPTOR SUBTYPES INVOLVED IN, AND TIME COURSE OF, THE LONG-TERM DESENSITIZATION OF GLUTAMATE RECEPTORS IN CEREBELLAR PURKINJE-CELLS

Desensitization of quisqualate (QA)-specific glutamate receptors of Purkinje cells was examined by 'wedge' recording from cerebellar slices. The desensitization was induced by conditioning with bath application of 100 μM QA for 4 min, and was represented by reduced responsiveness to testing QA applications. Bath application of 10 μM α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) for 1 min at a time had no effect on inducing desensitization, but AMPA responsiveness was reduced by the 4-min QA conditioning to the same extent as QA responsiveness. These results indicate that QA-induced desensitization in Purkinje cells takes place specifically in the ionotropic subtype of QA receptors which AMPA stimulates selectively, and further suggest that another metabotropic subtype of QA receptors which AMPA does not stimulate plays a role in inducing the desensitization. By using AMPA applications as neutral testings, the desensitization was followed for 2 h without sign of recovery. For intervals longer than 2 h, AMPA responsiveness was compared with responsiveness to a 1-min application of 3 mM aspartate (AS) as a control, since the latter was not affected by QA conditioning. The AMPA/AS responsiveness ratio remained reduced throughout 10 h after 4-min QA conditioning without sign of recovery. © 1990.