Journal of Neurophysiology, Vol 72, Issue 2 754-761, Copyright © 1994 by APS

ARTICLES

Regulation of glycine-insensitive desensitization of the NMDA receptor in outside-out patches

G. Tong and C. E. Jahr
Vollum Institute, Oregon Health Sciences University, 97201-3098.

1. Regulation of desensitization of N-methyl-D-aspartate (NMDA) receptors was studied in outside-out patches from cultured rat hippocampal neurons. The progressive increase in a glycine-insensitive form of desensitization after patch excision did not require extracellular Ca2+ concentration nor was it use dependent, but the initial extent of desensitization after patch formation was reduced by intracellular bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA). 2. Preincubation of neurons with 30 microM dantrolene, which can decrease Ca2+ release from intracellular stores, also reduced the degree of NMDA receptor desensitization just after patch excision. Thus the development of this form of desensitization appears to be triggered by a transient increase of intracellular calcium. 3. The extent of glycine-insensitive desensitization was also reduced by intracellular ATP-gamma S, high concentrations of the phosphatase inhibitor, microcystin, or intracellular application of a peptide inhibitor of calcineurin. These data support the hypothesis that glycine-insensitive desensitization of the NMDA receptor in outside-out patches is regulated in part by the phosphorylation state of the receptor or an associated protein. 4. Because the NMDA channel is very permeable to Ca2+, the extent of phosphorylation and thus desensitization of the receptors may be sensitive to synaptic activation and could serve as a feedback mechanism to decrease the intensity of excitation and plasticity.

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