{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:16:34Z","timestamp":1790468194560,"version":"4.1.0"},"reference-count":55,"publisher":"Rockefeller University Press","issue":"12","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":213,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication\n                                Disorders","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DC000273"],"award-info":[{"award-number":["R01 DC000273"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DC016318"],"award-info":[{"award-number":["R01 DC016318"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DC008130"],"award-info":[{"award-number":["R01 DC008130"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,12,2]]},"abstract":"<jats:p>The outer hair cell (OHC) of the organ of Corti underlies a process that enhances hearing, termed cochlear amplification. The cell possesses a unique voltage-sensing protein, prestin, that changes conformation to cause cell length changes, a process termed electromotility (eM). The prestin voltage sensor generates a capacitance that is both voltage- and frequency-dependent, peaking at a characteristic membrane voltage (Vh), which can be greater than the linear capacitance of the OHC. Accordingly, the OHC membrane time constant depends upon resting potential and the frequency of AC stimulation. The confounding influence of this multifarious time constant on eM frequency response has never been addressed. After correcting for this influence on the whole-cell voltage clamp time constant, we find that both guinea pig and mouse OHC eM is low pass, substantially attenuating in magnitude within the frequency bandwidth of human speech. The frequency response is slowest at Vh, with a cut-off, approximated by single Lorentzian fits within that bandwidth, near 1.5 kHz for the guinea pig OHC and near 4.3 kHz for the mouse OHC, each increasing in a U-shaped manner as holding voltage deviates from Vh. Nonlinear capacitance (NLC) measurements follow this pattern, with cut-offs about double that for eM. Macro-patch experiments on OHC lateral membranes, where voltage delivery has high fidelity, confirms low pass roll-off for NLC. The U-shaped voltage dependence of the eM roll-off frequency is consistent with prestin\u2019s voltage-dependent transition rates. Modeling indicates that the disparity in frequency cut-offs between eM and NLC may be attributed to viscoelastic coupling between prestin\u2019s molecular conformations and nanoscale movements of the cell, possibly via the cytoskeleton, indicating that eM is limited by the OHC\u2019s internal environment, as well as the external environment. Our data suggest that the influence of OHC eM on cochlear amplification at higher frequencies needs reassessment.<\/jats:p>","DOI":"10.1085\/jgp.201812280","type":"journal-article","created":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T18:55:19Z","timestamp":1572634519000},"page":"1369-1385","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Outer hair cell electromotility is low-pass filtered relative to the\n                    molecular conformational changes that produce nonlinear\n                    capacitance"],"prefix":"10.1085","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8274-7751","authenticated-orcid":true,"given":"Joseph","family":"Santos-Sacchi","sequence":"first","affiliation":[{"name":"Department of Surgery (Otolaryngology), Yale University School of Medicine, New Haven, CT 1"},{"name":"Department of Neuroscience, Yale University School of Medicine, New Haven, CT 2"},{"name":"Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9397-7704","authenticated-orcid":true,"given":"Kuni H.","family":"Iwasa","sequence":"additional","affiliation":[{"name":"National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-8991","authenticated-orcid":true,"given":"Winston","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Surgery (Otolaryngology), Yale University School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2019,11,1]]},"reference":[{"key":"2023122218144248900_bib1","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1113\/jphysiol.1987.sp016617","article-title":"A fast motile response in guinea-pig outer\n                        hair cells: the cellular basis of the cochlear amplifier","volume":"388","author":"Ashmore","year":"1987","journal-title":"J. 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