Thiocyanate stabilizes AMPA binding to the quisqualate receptor

Calcium and chloride ions stimulated [3H]glutamate binding to quisqualate-sensitive [3H]glutamate binding sites 4-fold, as measured by quantitative autoradiography, whereas 100 mM potassium thiocyanate had no additional effect. In contrast, calcium and chloride had little effect on the binding of [3H](RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA), but 100 mM thiocyanate stimulated binding 4-fold. AMPA displaced little [3H]glutamate binding from quisqualate-sensitive binding sites in the molecular layer of the cerebellum in the absence of thiocyanate. However, in the presence of thiocyanate AMPA became a more effective displacer, but still displaced only 44% of the quisqualate-sensitive [3H]glutamate binding. The distribution of [3H]glutamate binding to quisqualate-sensitive sites was similar to but not identical with that of [3H]AMPA binding. However, the distribution of AMPA-displaceable [3H]glutamate binding correlated highly (r = 0.97, P less than 0.0005) with that of [3H]AMPA binding. The results suggest that AMPA binds to a subclass of quisqualate-sensitive [3H]glutamate binding sites that are highly influenced by ionic environment and that quisqualate-sensitive binding sites exist in several states.