Evidence that high- and low-affinity DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding sites reflect membrane-dependent states of a single receptor.

Binding of DL-alpha-[3H]amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ([3H]AMPA) to lysed rat brain membranes in the presence of potassium thiocyanate resulted in curvilinear Scatchard plots that could be resolved by regression analysis into a large low-affinity component and a small high-affinity component. Solubilization with Triton X-100 resulted in solubilized and nonsolubilized fractions that were considerably enriched in the high-affinity component and correspondingly reduced in the low-affinity component. It thus appears that solubilization converts low-affinity AMPA receptors into high-affinity receptors. Also, synaptic plasma membranes were found to be greatly enriched in the low-affinity form and deficient in the high-affinity form of the AMPA receptor. These experiments provide evidence for the hypothesis that the high- and low-affinity components of AMPA binding are interconvertible states of the same receptor rather than separate binding sites and that the conversion of these receptors from their native high-affinity state to the low-affinity state occurs on insertion of the receptors into synapses.