TRPA1 activation in non-sensory supporting cells contributes to regulation of cochlear sensitivity after acoustic trauma.

TRPA1 activation in non-sensory supporting cells contributes to regulation of cochlear sensitivity after acoustic trauma.
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DOI:
10.1038/s41467-023-39589-w
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发表时间:
2023-06-30
影响因子:
16.6
通讯作者:
Frolenkov, Gregory I.
Frolenkov, Gregory I.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Velez-Ortega, A. Catalina;Stepanyan, Ruben;Edelmann, Stephanie E.;Torres-Gallego, Sara;Park, Channy;Marinkova, Desislava A.;Nowacki, Joshua S.;Sinha, Ghanshyam P.;Frolenkov, Gregory I.

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TRPA 1通道在伤害感受神经元中表达,在那里它们检测伤害性刺激,并且在哺乳动物耳蜗中表达,在那里它们的功能是未知的。在这里,我们表明,TRPA 1在支持非感觉Hensen的细胞的小鼠耳蜗激活引起延长的Ca 2+反应,传播整个器官的Corti和柱和Deiters细胞引起持久的收缩。笼状Ca ~(2+)实验表明,类似于Deiters细胞,柱细胞也具有Ca ~(2+)依赖性收缩机制。TRPA 1通道被氧化应激和细胞外ATP的内源性产物激活。由于这两种刺激都存在于声创伤后的体内,因此噪声后TRPA 1的激活可能会通过支持细胞收缩来影响耳蜗敏感性。TRPA 1缺陷导致噪声引起的听阈暂时性偏移较大,但持续时间较短,并伴有听性脑干反应潜伏期的永久性变化。我们的结论是,TRPA 1有助于调节耳蜗敏感性的声损伤后。TRPA 1通道在哺乳动物耳蜗中的功能知之甚少。在这里,作者表明,Corti器官支持细胞中的TRPA 1通道介导了收缩反应,这可能有助于小鼠在噪声暴露后听力阈值的暂时变化。
TRPA1 channels are expressed in nociceptive neurons, where they detect noxious stimuli, and in the mammalian cochlea, where their function is unknown. Here we show that TRPA1 activation in the supporting non-sensory Hensen’s cells of the mouse cochlea causes prolonged Ca2+ responses, which propagate across the organ of Corti and cause long-lasting contractions of pillar and Deiters’ cells. Caged Ca2+ experiments demonstrated that, similar to Deiters’ cells, pillar cells also possess Ca2+-dependent contractile machinery. TRPA1 channels are activated by endogenous products of oxidative stress and extracellular ATP. Since both these stimuli are present in vivo after acoustic trauma, TRPA1 activation after noise may affect cochlear sensitivity through supporting cell contractions. Consistently, TRPA1 deficiency results in larger but less prolonged noise-induced temporary shift of hearing thresholds, accompanied by permanent changes of latency of the auditory brainstem responses. We conclude that TRPA1 contributes to the regulation of cochlear sensitivity after acoustic trauma. The function of TRPA1 channels in the mammalian cochlea is poorly understood. Here, the authors show that TRPA1 channels in supporting cells of the organ of Corti mediate contractile responses that may contribute to temporary shifts in hearing thresholds after noise exposure in mice.
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