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Fyn Tyrosine Kinase Reduces the Ethanol Inhibition of Recombinant NR1/NR2A but Not NR1/NR2B NMDA Receptors Expressed in HEK 293 Cells
Author(s) -
Anders Douglas L.,
Blevins Tana,
Sutton Greg,
Swope Sheridan,
Chandler L. Judson,
Woodward John J.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.721389.x
Subject(s) - fyn , tyrosine phosphorylation , src family kinase , tyrosine kinase , receptor , phosphorylation , chemistry , tyrosine , proto oncogene tyrosine protein kinase src , biochemistry , nmda receptor , microbiology and biotechnology , biology , pharmacology
NMDA receptors are potentiated by phosphorylation in a subunit‐ and kinase‐specific manner. Both native and recombinant NMDA receptors are inhibited by behaviorally relevant concentrations of ethanol. Whether the phosphorylation state of individual subunits modulates the ethanol sensitivity of these receptors is not known. In this study, the effects of Fyn tyrosine kinase on the ethanol sensitivity of specific recombinant NMDA receptors expressed in HEK 293 cells were investigated. Whole‐cell mode patch clamp and ratiometric calcium imaging demonstrated that the degree of ethanol inhibition of NR1/NR2B receptors was unaffected by Fyn tyrosine kinase. In contrast, the inhibition of NR1/NR2A receptors by ethanol (100 m M ) was significantly reduced under conditions of enhanced Fyn‐mediated tyrosine phosphorylation of the NR2A subunit. This effect was not observed at lower concentrations of ethanol (≤ 50 m M ). These results suggest that tyrosine phosphorylation of specific NMDA receptors by Fyn tyrosine kinase may regulate the sensitivity of these receptors to the sedative/hypnotic concentrations of ethanol.