Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation
Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation
复制标题
水杨酸钠对耳蜗内毛细胞钙电流和胞吐作用的影响：对耳鸣产生的影响
DOI：
10.1007/s12264-021-00747-z
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发表时间：
2021-07-07
影响因子：
5.6
通讯作者：
Li, Jian
中科院分区：
文献类型：
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作者：
Fan, Ting;Xiang, Meng-Ya;Li, Jian
水杨酸钠是一种抗炎药物，有耳鸣的副作用。在这里，我们使用小鼠耳蜗培养来探讨水杨酸处理对耳蜗内毛细胞(IHC)的影响。我们发现，在暴露于高浓度水杨酸盐后，IHC显示出显著的损伤。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，提示IHC不是通过增强神经元的输入参与耳鸣的发生。相反，水杨酸盐引起更大的峰值幅度、更负的半激活电压和更陡峭的钙电流斜率因子。利用钙离子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钙通道的数量，并伴随着CaV1.3的表达。所有这些变化可以协同作用，促进钙离子内流到IHC。抑制细胞内钙超载可显著减轻10 mmol/L水杨酸处理后IHC的死亡。这些结果暗示了外周听觉系统中耳鸣产生的细胞机制。
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.