Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells:Implications for Tinnitus Generation  

作　　者：Ting Fan Meng-Ya Xiang Ruo-Qiao Zhou Wen Li Li-Qin Wang Peng-Fei Guan Geng-Lin Li Yun-Feng Wang Jian Li 

机构地区：[1]ENT Institute and Department of Otorhinolaryngology,EYE&ENT Hospital,Fudan University,Shanghai,200031,China [2]NHC Key Laboratory of Hearing Medicine,Fudan University,Shanghai,200031,China [3]Clinical Laboratory Center,Children’s Hospital of Fudan University,Shanghai,201102,China

出　　处：《Neuroscience Bulletin》2022年第1期69-80,共12页神经科学通报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(81770999 and 81670281);the Shanghai Municipal Commission of Science and Technology Research Project(18140900304,and 19140900902);the Big Data and Artificial Intelligence Project(2020DSJ07).

摘　　要：Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus.Here,we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells(IHCs).We found that IHCs showed significant damage after exposure to a high concentration of salicylate.Whole-cell patch clamp recordings showed that 1–5 mmol/L salicylate did not affect the exocytosis of IHCs,indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input.Instead,salicylate induced a larger peak amplitude,a more negative half-activation voltage,and a steeper slope factor of Ca^(2+)current.Using noise analysis of Ca^(2+)tail currents and qRT-PCR,we further found that salicylate increased the number of Ca^(2+)channels along with CaV1.3 expression.All these changes could act synergistically to enhance the Ca^(2+)influx into IHCs.Inhibition of intracellular Ca^(2+)overload significantly attenuated IHC death after 10 mmol/L salicylate treatment.These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.

关 键 词：SALICYLATE TINNITUS Inner hair cell Calcium current EXOCYTOSIS Whole-cell patch clamp CaV1.3 channel 

分 类 号：R764[医药卫生—耳鼻咽喉科]