{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:39:27Z","timestamp":1791275967368,"version":"4.1.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,4,30]]},"abstract":"<jats:p>\n                    The sense of hearing is remarkable for its auditory dynamic range, which spans more than 10\n                    <jats:sup>12<\/jats:sup>\n                    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\n                    <jats:sub>2<\/jats:sub>\n                    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\n                    <jats:italic>P2RX2<\/jats:italic>\n                    gene (encoding the P2X\n                    <jats:sub>2<\/jats:sub>\n                    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\n                    <jats:sub>2<\/jats:sub>\n                    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\n                    <jats:italic>P2RX2-<\/jats:italic>\n                    null mice. At higher sound levels (\u226595 dB), additional processes dominated TTS, and\n                    <jats:italic>P2RX2-<\/jats:italic>\n                    null mice were more vulnerable than WT mice to permanent hearing loss due to hair cell synapse disruption.\n                    <jats:italic>P2RX2-<\/jats:italic>\n                    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\n                    <jats:sub>2<\/jats:sub>\n                    receptor-dependent purinergic hearing adaptation that underpins the upper physiological range of hearing.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1222295110","type":"journal-article","created":{"date-parts":[[2013,4,16]],"date-time":"2013-04-16T23:05:59Z","timestamp":1366153559000},"page":"7494-7499","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":116,"title":["ATP-gated ion channels mediate adaptation to elevated sound levels"],"prefix":"10.1073","volume":"110","author":[{"given":"Gary D.","family":"Housley","sequence":"first","affiliation":[{"name":"Department of Physiology and Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;"},{"name":"Department of Physiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Morton-Jones","sequence":"additional","affiliation":[{"name":"Department of Physiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srdjan M.","family":"Vlajkovic","sequence":"additional","affiliation":[{"name":"Department of Physiology,"},{"name":"Centre for Brain Research, School of Medical Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindra S.","family":"Telang","sequence":"additional","affiliation":[{"name":"Department of Physiology,"},{"name":"Centre for Brain Research, School of Medical Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinthiya","family":"Paramananthasivam","sequence":"additional","affiliation":[{"name":"Department of Physiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif F.","family":"Tadros","sequence":"additional","affiliation":[{"name":"Department of Physiology and Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann Chi Yan","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Physiology and Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina E.","family":"Froud","sequence":"additional","affiliation":[{"name":"Department of Physiology and Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie M. E.","family":"Cederholm","sequence":"additional","affiliation":[{"name":"Department of Physiology and Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogeesan","family":"Sivakumaran","sequence":"additional","affiliation":[{"name":"Department of Physiology and Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peerawuth","family":"Snguanwongchai","sequence":"additional","affiliation":[{"name":"Department of Physiology and Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baljit S.","family":"Khakh","sequence":"additional","affiliation":[{"name":"Departments of dPhysiology and"},{"name":"Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra A.","family":"Cockayne","sequence":"additional","affiliation":[{"name":"Boston Scientific, San Jose, CA 95134;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Thorne","sequence":"additional","affiliation":[{"name":"Department of Physiology,"},{"name":"Centre for Brain Research, School of Medical Sciences, and"},{"name":"Section of Audiology, School of Population Health, University of Auckland, Auckland 1142, New Zealand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen F.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Departments of hSurgery and"},{"name":"Neurosciences, University of California at San Diego, Ja Jolla, CA 92037; and"},{"name":"San Diego Veterans Administration Medical Center, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,4,16]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1088\/0964-1726\/21\/6\/064001"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(99)00223-3"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/1084713810381771"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01050.2011"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08654.x"},{"key":"e_1_3_3_6_2","unstructured":"; Secretary of State UK (2005) The Control of Noise at Work Regulations Health and Safety (Secretary of State UK) Statutory Instruments no. 1643. 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