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 Ca_V1.3 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.

水杨酸钠是一种具有耳鸣副作用的抗炎药。在这里，我们使用小鼠耳蜗培养物来探索水杨酸盐处理对耳蜗内毛细胞 (IHC) 的影响。我们发现 IHC 在接触高浓度水杨酸盐后表现出明显的损伤。全细胞膜片钳记录显示 1–5 mmol/L 水杨酸盐不影响 IHC 的胞吐作用，表明 IHC 不通过增强其神经元输入参与耳鸣的产生。相反，水杨酸盐诱导了更大的峰值振幅、更负的半激活电压和更陡峭的 Ca ²⁺电流斜率因子。^{使用 Ca 2+}尾电流的噪声分析和 qRT-PCR，我们进一步发现水杨酸盐增加了 Ca ^2+的数量通道以及 Ca _V 1.3 表达。所有这些变化都可以协同作用以增强 Ca ²⁺流入 IHC。10 mmol/L 水杨酸盐处理后，细胞内 Ca ²⁺超载的抑制显着减弱了 IHC 死亡。这些结果暗示了周围听觉系统中耳鸣产生的细胞机制。