ATP-gated ion channels mediate adaptation to elevated sound levels
ATP-gated ion channels mediate adaptation to elevated sound levels
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DOI：
10.1073/pnas.1222295110
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发表时间：
2013-04-30
影响因子：
11.1
通讯作者：
Ryan, Allen F.
中科院分区：
文献类型：
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作者：
Housley, Gary D.;Morton-Jones, Rachel;Ryan, Allen F.
听觉的听觉动态范围是显著的，其声强跨度超过1012。使耳蜗能够在没有损伤的情况下获得高声级的机制是关键的兴趣，特别是关于工业，军事和娱乐听觉过度刺激对听力残疾的广泛影响。我们发现，由耳蜗中的P2 X（2）受体亚基组装的ATP门控离子通道对于暂时性阈值偏移（TTS）的发展是必要的，这在听觉脑干反应记录中是明显的。在P2 RX 2基因（编码P2 X（2）受体亚基）缺失的小鼠中，持续85 dB的噪音不能引起野生型小鼠出现的TTS。随着声级的升高，耳蜗分区组织释放的ATP可能会激活内淋巴室上皮细胞上广泛分布的P2 X（2）受体。与P2 RX 2缺失小鼠相比，WT小鼠中噪声诱导的对来自外毛细胞转导的畸变产物耳声发射的抑制显著更大，并且阈值上听觉脑干反应输入/输出增益降低，从而支持了这种嘌呤能信号传导。在更高的声级（>= 95 dB），额外的过程占主导地位的TTS，和P2 RX 2-null小鼠比野生型小鼠更容易永久性听力损失，由于毛细胞突触破坏。P2 RX 2基因敲除小鼠缺乏跨耳蜗分区的ATP门控电导，包括毛细胞中ATP门控内向电流的丧失。这些数据表明，TTS的一个重要组成部分代表P2 X（2）受体依赖性嘌呤能听力适应，支持听力的生理范围上限。
The sense of hearing is remarkable for its auditory dynamic range, which spans more than 1012 in acoustic intensity. The mechanisms that enable the cochlea to transduce high sound levels without damage are of key interest, particularly with regard to the broad impact of industrial, military, and recreational auditory overstimulation on hearing disability. We show that ATP-gated ion channels assembled from P2X(2) receptor subunits in the cochlea are necessary for the development of temporary threshold shift (TTS), evident in auditory brainstem response recordings as sound levels rise. In mice null for the P2RX2 gene (encoding the P2X(2) receptor subunit), sustained 85-dB noise failed to elicit the TTS that wild-type (WT) mice developed. ATP released from the tissues of the cochlear partition with elevation of sound levels likely activates the broadly distributed P2X(2) receptors on epithelial cells lining the endolymphatic compartment. This purinergic signaling is supported by significantly greater noise-induced suppression of distortion product otoacoustic emissions derived from outer hair cell transduction and decreased suprathreshold auditory brainstem response input/output gain in WT mice compared with P2RX2-null mice. At higher sound levels (>= 95 dB), additional processes dominated TTS, and P2RX2-null mice were more vulnerable than WT mice to permanent hearing loss due to hair cell synapse disruption. P2RX2-null mice lacked ATP-gated conductance across the cochlear partition, including loss of ATP-gated inward current in hair cells. These data indicate that a significant component of TTS represents P2X(2) receptordependent purinergic hearing adaptation that underpins the upper physiological range of hearing.