Fyn tyrosine kinase reduces the ethanol inhibition of recombinant NR1/NR2Abut 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 b y behaviorally relevant concentrations of ethanol, Whether the phosphorylat ion 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 ratiom etric 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 red uced under conditions of enhanced Fyn-mediated tyrosine phosphorylation of the NR2A subunit. This effect was not observed at lower concentrations of e thanol (less than or equal to 50 mM). These results suggest that tyrosine p hosphorylation of specific NMDA receptors by Fyn tyrosine kinase may regula te the sensitivity of these receptors to the sedative/hypnotic concentratio ns of ethanol.