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Journal of Comparative Physiology A

, Volume 205, Issue 4, pp 469–479 | Cite as

Neurotoxicity of sodium salicylate to the spiral ganglion neurons: GABAA receptor regulates NMDA receptor by Fyn-dependent phosphorylation

  • Peiqiang Liu
  • Danxue Qin
  • Xi Huang
  • Huiying Chen
  • Wenhua Ye
  • Xiaoyu Lin
  • Jiping SuEmail author
Original Paper
  • 56 Downloads

Abstract

The purpose of this study was to observe the regulatory effects of GABAA (γ-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 GABAA 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 GABAA receptor. These results suggest that the modified pattern of dynamic balance between excitation and inhibition by coactivation of the GABAA receptor can attenuate the excitatory NMDA receptor under the action of SS, via inhibiting the Fyn-dependent phosphorylation of Y1472.

Keywords

Sodium salicylate Spiral ganglion neurons GABAANMDAR Neurotoxicity 

Abbreviations

Bic

Bicuculline

GABAA

Receptor agonist

CK2

Casein Kinase 2

GABAAR

γ-Aminobutyric acid A receptor

Mus

Muscimol, GABAA receptor antagonist

NMDAR

N-Methyl-d-aspartate receptor

NR2B

NMDA receptor 2B subunit

PP2

4-Amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine

RQ

Relative quantity

SGNs

Spiral ganglion neurons

SS

Sodium salicylate

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC) (81360157, 81560174). We also thank the help from the Medical Scientific Research Center of Guangxi Medical University, and the Experimental Animal Center of Guangxi Medical University. All procedures performed in studies involving animals were in accordance with the ethical standards of the NSFC guidelines for the care and use of animals, as described in the “Materials and methods” section.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Peiqiang Liu
    • 1
  • Danxue Qin
    • 1
  • Xi Huang
    • 1
    • 2
  • Huiying Chen
    • 1
  • Wenhua Ye
    • 1
  • Xiaoyu Lin
    • 1
  • Jiping Su
    • 1
    Email author
  1. 1.Department of Otolaryngology-Head and Neck SurgeryFirst Affiliated Hospital of Guangxi Medical UniversityNanningChina
  2. 2.Department of Otolaryngology-Head and Neck SurgeryWuhan No. 1 HospitalWuhanChina

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