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M Baudry, K Kramer and G Lynch
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.