TRPA1在豚鼠前庭外周的功能性表达及其参与庆大霉素前庭毒性作用的机制研究

The transient receptor potential channel A1 (TRPA1) is a subtribe of TRP channels family, and it plays an important role in the pain, temperature sensation, and the intracellular calcium signal transduction in mammals. Studies have reported TRPA1 was expressed in vestibular hair cells of the inner ear in mammals, but whether it is functional expression and its function are still unclear. Our previous studies have found that the TRPA1 current could be recorded on vestibular hair cells in guinea pig, and gentamicin could inhibit it reversibly. These results indicated that TRPA1 was functional expression on vestibular periphery of guinea pig and it might participate in vestibulotoxicity of gentamicin. Therefore, this project aimed to vertify the functional expression of TRPA1 on vestibular hair cells of guinea pig and study the mechanism of its participation in acute vestibulotoxicity of gentamicin by electrophysiological method. Meanwhile, by using tracer of gentamicin, whether TRPA1 could mediate gentamicin into the vestibular hair cells in vitro and in vivo was studied, it would provide evidence for the involvement of TRPA1 in the chronic vestibulotoxicity of gentamicin, and provide evidence and new targets for prevention and treatment of gentamicin vestibulotoxicity.

瞬时受体电位通道A1（TRPA1）是TRP通道家族的一个亚族，在哺乳动物的痛觉、温度觉传递和细胞内钙信号转导中发挥重要作用。有研究报道TRPA1在哺乳动物内耳前庭毛细胞上有表达，但其是否有功能以及有何功能仍不清楚。我们前期研究发现在豚鼠前庭毛细胞上可记录到TRPA1电流，且能被庆大霉素可逆性抑制，提示TRPA1在豚鼠前庭外周为功能性表达，并且可能参与庆大霉素的前庭毒性作用。因此，本项目拟采用电生理学方法验证TRPA1在豚鼠前庭毛细胞上为功能性表达，并深入研究其参与庆大霉素急性前庭毒性作用的机制，同时选择示踪剂来观察TRPA1能否介导庆大霉素进入离体和在体的前庭毛细胞，为TRPA1参与庆大霉素慢性前庭毒性作用提供证据，也为庆大霉素前庭毒性的防治提供理论依据和新的干预靶点。