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

G. Tong, Craig Jahr

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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 μM 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-γ-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.

Original languageEnglish (US)
Pages (from-to)754-761
Number of pages8
JournalJournal of Neurophysiology
Volume72
Issue number2
StatePublished - 1994

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N-Methyl-D-Aspartate Receptors
Glycine
Phosphorylation
Dantrolene
Neurons
N-Methylaspartate
Phosphoric Monoester Hydrolases
Adenosine Triphosphate
Calcium
Peptides
Acids
Proteins

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Regulation of glycine-insensitive desensitization of the NMDA receptor in outside-out patches. / Tong, G.; Jahr, Craig.

In: Journal of Neurophysiology, Vol. 72, No. 2, 1994, p. 754-761.

Research output: Contribution to journalArticle

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N2 - 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 μM 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-γ-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.

AB - 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 μM 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-γ-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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