Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation
Ting Fan1,2 • Meng-Ya Xiang1,2 • Ruo-Qiao Zhou1,2 • Wen Li1,2 • Li-Qin Wang1 • Peng-Fei Guan1,2 • Geng-Lin Li1 • Yun-Feng Wang1,2 • Jian Li3
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
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 Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ 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.
Salicylate; Tinnitus; Inner hair cell; Calcium current; Exocytosis; Whole-cell patch clamp; CaV1.3 channel