Regulation by calcium ions of glutamate receptor binding in hippocampal slices.
Hippocampal slices were incubated in a Krebs-bicarbonate buffer with various concentrations of calcium and [3H]glutamate receptor binding was measured in crude synaptic membranes derived from these slices. Increasing the calcium concentration from 0 to 2.5 mM resulted in a 2.2-fold increase in the maximal number of the Na-independent [3H]glutamate binding sites without changes in their affinity for [3H]glutamate. This effect was totally blocked by the addition of the protease inhibitor leupeptin (50 microM) to the slice incubation medium. No effect was observed on the Na-dependent [3H]glutamate binding nor on the Na-independent [ 3H ]glutamate binding measured in the presence of a concentration of calcium of 250 microM. Increasing the calcium concentration also resulted in an increased proteolytic activity which was inhibited by about 70% by the addition of leupeptin. Finally, increasing the calcium concentration induced the degradation of high-molecular weight proteins, the microtubule-associated proteins (MAPs) and the 220 000 dalton doublet protein corresponding to fodrin. Both effects were partially prevented by the addition of leupeptin in the slice incubation medium. These results indicate that the same calcium-dependent processes which were previously shown to regulate [ 3H ]glutamate receptor binding to hippocampal membranes occur in the hippocampal slice preparation, and they suggest a mechanism by which fluctuations in calcium levels can activate a calcium-dependent proteinase, the degradation of cytoskeletal-associated proteins and the unmasking of additional glutamate receptors. The participation of such processes in various forms of plasticity is discussed.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D005971:Glutamates / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008970:Molecular Weight; D010447:Peptide Hydrolases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017470:Receptors, Glutamate
D005971:Glutamates; D011956:Receptors, Cell Surface; D017470:Receptors, Glutamate; D010447:Peptide Hydrolases; D002118:Calcium