Neurotoxicity of sodium salicylate to the spiral ganglion neurons: GABA(A) receptor regulates NMDA receptor by Fyn-dependent phosphorylation

摘要

The purpose of this study was to observe the regulatory effects of GABA(A) (gamma-aminobutyric acid A) receptor on the N-methyl-d-aspartate (NMDA) receptor during excitotoxicity in spiral ganglion neurons in the rat cochlea induced by sodium salicylate (SS). Western blot illustrated SS decreased the expression of NMDA receptor 2B subunit (NR2B) surface protein through affecting GABA(A) receptor, but the total protein content did not significantly change. Y1472 and S1480 are important phosphorylation sites in NR2B, SS downregulated the Fyn-dependent phosphorylation of Y1472 in a manner not related to the CK2 (Casein Kinase 2) dependent phosphorylation of S1480, thus regulating the surface distribution and internalization of NMDA receptor through GABA(A) receptor. These results suggest that the modified pattern of dynamic balance between excitation and inhibition by coactivation of the GABA(A) receptor can attenuate the excitatory NMDA receptor under the action of SS, via inhibiting the Fyn-dependent phosphorylation of Y1472.