Classification and properties of acidic amino acid receptors in hippocampus. III. Supersensitivity during the postnatal period and following denervation.

The effects of excitatory amino acids on 22Na efflux rate in rat hippocampal slices were determined at various postnatal days and following removal of a major afferent system. Two weeks after a unilateral hippocampal aspiration, the 22Na efflux induced by potassium ions, D-glutamate, N-methylaspartate, and kainate is significantly decreased in the contralateral intact hippocampus whereas the effect of L-glutamate is substantially increased. Analysis of concentration-response curves suggests that the increased responsiveness to L-glutamate is due to an increase in the maximal effect rather than to changes in the half-maximal concentration for the amino acid. Partial denervation does not detectably change efflux elicited by D,L-homocysteic acid nor does it modify the properties of [3H]glutamate binding to hippocampal membranes. The effects of potassium ions, N-methylaspartate, and kainate but not of D,L-homocysteate are significantly decreased in slices incubated in the absence of calcium. All of the amino acids tested are considerably more potent in slices prepared from 11-day-old rats than in those from adult rats; the differences in responsiveness reflect an increase in maximal effect without changes in the half-maximal concentration. The responses to L-glutamate and D,L-homocysteate decline steadily between postnatal days 11 and 30, at which time adult values are reached. Together, the results from the denervation and development studies suggest a different localization and different modes of regulation for various classes of excitatory amino acid receptors.