Regulation of glycine-insensitive desensitization of the NMDA receptor in outside-out patches.
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.
Tong
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Vollum Institute, Oregon Health Sciences University, 97201-3098.
Jahr
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D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D046508:Culture Techniques; D005246:Feedback / Q000502:physiology; D005998:Glycine / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium; D005998:Glycine