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PMID: 8643696 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Ca(2+)-independent reduction of N-methyl-D-aspartate channel activity by protein tyrosine phosphatase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 4 ·1996-02-20 ·Pages 1721-5

Wang YT, Yu XM, Salter MW

Abstract

Regulation of ion channel function by intracellular processes is fundamental for controlling synaptic signaling and integration in the nervous system. Currents mediated by N-methyl-D-aspartate (NMDA) receptors decline during whole-cell recordings and this may be prevented by ATP. We show here that phosphorylation is necessary to maintain NMDA currents and that the decline is not dependent upon Ca2+. A protein tyrosine phosphatase or a peptide inhibitor of protein tyrosine kinase applied intracellularly caused a decrease in NMDA currents even when ATP was included. On the other hand, pretreating the neurons with a membrane-permeant tyrosine kinase inhibitor occluded the decline in NMDA currents when ATP was omitted. In inside-out patches, applying a protein tyrosine phosphatase to the cytoplasmic face of the patch caused a decrease in probability of opening of NMDA channels. Conversely, open probability was increased by a protein tyrosine phosphatase inhibitor. These results indicate that NMDA channel activity is reduced by a protein tyrosine phosphatase associated with the channel complex.

MeSH Terms
Adenosine Triphosphate/analogs & derivatives,pharmacology Adenylyl Imidodiphosphate/pharmacology Animals Calcium/physiology Cells, Cultured Down-Regulation/drug effects Egtazic Acid/analogs & derivatives,pharmacology Enzyme Inhibitors/pharmacology Genistein Ion Channel Gating/drug effects Ion Channels/drug effects,metabolism Isoflavones/pharmacology Oncogene Protein pp60(v-src)/pharmacology Patch-Clamp Techniques Peptide Fragments/pharmacology Phosphorylation Protein Processing, Post-Translational Protein Tyrosine Phosphatases/antagonists & inhibitors,pharmacology Proto-Oncogene Proteins pp60(c-src)/pharmacology Rats Rats, Wistar Receptors, N-Methyl-D-Aspartate/drug effects,metabolism Spinal Cord/cytology
Chemicals
Enzyme Inhibitors Ion Channels Isoflavones Peptide Fragments Receptors, N-Methyl-D-Aspartate peptide A Adenylyl Imidodiphosphate adenosine 5'-O-(3-thiotriphosphate) Egtazic Acid Adenosine Triphosphate Genistein Oncogene Protein pp60(v-src) Proto-Oncogene Proteins pp60(c-src) Protein Tyrosine Phosphatases 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wang Y T
Division of Neuroscience, Hospital for Sick Children, Toronto, Canada.
Yu X M
Salter M W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.4.1721
Published
1996-02-20
Pages
1721-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC40009
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.93.4.1721 PMC Full Text View journal details
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