Fyn tyrosine kinase reduces the ethanol inhibition of recombinant NR1/NR2A but not NR1/NR2B NMDA receptors expressed in HEK 293 cells.
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 mM) 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 (< or = 50 mM). 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.
Anders
D L
DL
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Blevins
T
T
Sutton
G
G
Swope
S
S
Chandler
L J
LJ
Woodward
J J
JJ
D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000166:cytology; D008967:Molecular Biology; D018408:Patch-Clamp Techniques; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D051076:Proto-Oncogene Proteins c-fyn; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics; D014162:Transfection
D002492:Central Nervous System Depressants; D011518:Proto-Oncogene Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D000431:Ethanol; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn