当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > ATP-gated ion channels mediate adaptation to elevated sound levels.

ATP-gated ion channels mediate adaptation to elevated sound levels.

Abstract：

:The sense of hearing is remarkable for its auditory dynamic range, which spans more than 10(12) 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 P2X2 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 P2X2 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 P2X2 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 P2X2 receptor-dependent purinergic hearing adaptation that underpins the upper physiological range of hearing.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Housley GD,Morton-Jones R,Vlajkovic SM,Telang RS,Paramananthasivam V,Tadros SF,Wong AC,Froud KE,Cederholm JM,Sivakumaran Y,Snguanwongchai P,Khakh BS,Cockayne DA,Thorne PR,Ryan AF

doi

10.1073/pnas.1222295110

subject

Has Abstract

pub_date

2013-04-30 00:00:00

pages

7494-9

issue

eissn

0027-8424

issn

1091-6490

pii

1222295110

journal_volume

110

pub_type

杂志文章

在线工具

ATP-gated ion channels mediate adaptation to elevated sound levels.