Prestin-based outer hair cell electromotility in knockin mice does not appear to adjust the operating point of a cilia-based amplifier

Gao, Jiangang; Wang, Xiang; Wu, Xudong; Aguiñaga, Sal; Huynh, K. H.; Song, Jia; Matsuda, Keiji; Patel, M. N.; Zheng, Jing; Cheatham, Mary Ann; He, David Z.Z.; Dallos, Peter; Zuo, Jian

doi:10.1073/pnas.0700356104

Cited by 36 publications

(48 citation statements)

References 41 publications

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“…Such computations have provided good estimates for WT-/Cl-prestin heteromers (Ϫ99 Ϯ 14 mV predicted versus Ϫ94 Ϯ 12 mV actual measurement; Ref. 32) and for D154N/D342Q prestin heteromers (Ϫ49 Ϯ 14 mV predicted versus Ϫ43 Ϯ 4 mV actual measurement; Ref. 12).…”

Section: Discussionmentioning

confidence: 97%

The V499G/Y501H Mutation Impairs Fast Motor Kinetics of Prestin and Has Significance for Defining Functional Independence of Individual Prestin Subunits

Homma

Duan

Zheng

et al. 2013

Journal of Biological Chemistry

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Background: Prestin converts electrical energy into mechanical work. Results: The V499G/Y501H mutation significantly impairs fast motor kinetics of prestin. Conclusion: Impaired kinetics is attributable to mutation at the Val-499 site that is conserved among SLC26 proteins regardless of their function as motors or transporters. Significance: V499G/Y501H mutated prestin provides clues to the molecular mechanisms underlying somatic electromotility and thus cochlear amplification.

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Section: Discussionmentioning

confidence: 97%

The V499G/Y501H Mutation Impairs Fast Motor Kinetics of Prestin and Has Significance for Defining Functional Independence of Individual Prestin Subunits

Homma

Duan

Zheng

et al. 2013

Journal of Biological Chemistry

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“…When K233Q/K235Q/R236Q (C1) mutations were introduced into the prestin locus, the targeting construct possessed a floxed Neo selection marker in intron 6. 2 of 6 homologous recombinant ES cell clones showed no C1 mutations but had the Neo cassette inserted into intron 6 in an orientation opposite to that of the prestin locus [10]. These prestinNeo mice were crossed with prestin -/-mice [2] to produce both homozygous prestinNeo knock-in mice (neo/neo) and mice with a Neo allele and a prestin knock-out allele (neo/-).…”

Section: Resultsmentioning

confidence: 99%

Normal Hearing Sensitivity at Low to Middle Frequencies with ∼25% Prestin

Zuo¹,

Yamashita²,

Fang³

et al. 2011

AIP Conference Proceedings

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Abstract. Two mechanisms have been proposed for outer hair cell (OHC)-mediated amplification in the mammalian cochlea: hair-bundle motility and somatic, prestin-based, motility. In cochlear mechanical modeling, different amounts of OHC-motor activity should provide different degrees of feedback efficiency and gain of the amplifier at resonant frequencies. We created two novel knock-in prestin mice with reduced quantities (∼25% and 50%) of prestin. OHCs from these mice exhibited length, non-linear capacitance (NLC) and electromotility values intermediate between wild-type and prestin knock-out mice. Surprisingly, hearing sensitivity up to 22 kHz of knock-in and wildtype mice are similar, so ∼25% prestin is sufficient for normal hearing at these frequencies. In these mice in the mentioned frequency range, OHC NLC and electromotility do not correlate with in vivo gain of the cochlear amplifier as predicted by the feedback model of the OHC motor.

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“…Electromotility operates so swiftly that it seems likely to play an important role in the active process (Frank et al 1999;Gale and Ashmore 1997); moreover, the absence of prestin or severe modification of its range of voltage sensitivity abrogates the active process (Cheatham et al 2004;Dallos et al 2008;Gao et al 2007;Liberman et al 2002). Electromotility is nearly linear over the physiological range of receptor potentials, however, and displays no frequency tuning; it thus seems unable by itself to account for the properties of the active process.…”

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confidence: 99%

A Critique of the Critical Cochlea: Hopf—a Bifurcation—Is Better Than None

Hudspeth

Jülicher

Martin

2010

Journal of Neurophysiology

119

126

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Hudspeth AJ, Jülicher F, Martin P. A critique of the critical cochlea: Hopf-a bifurcation-is better than none. J Neurophysiol 104: 1219-1229. First published June 10, 2010 doi:10.1152/jn.00437.2010. The sense of hearing achieves its striking sensitivity, frequency selectivity, and dynamic range through an active process mediated by the inner ear's mechanoreceptive hair cells. Although the active process renders hearing highly nonlinear and produces a wealth of complex behaviors, these various characteristics may be understood as consequences of a simple phenomenon: the Hopf bifurcation. Any critical oscillator operating near this dynamic instability manifests the properties demonstrated for hearing: amplification with a specific form of compressive nonlinearity and frequency tuning whose sharpness depends on the degree of amplification. Critical oscillation also explains spontaneous otoacoustic emissions as well as the spectrum and level dependence of the ear's distortion products. Although this has not been realized, several valuable theories of cochlear function have achieved their success by incorporating critical oscillators.The technical specifications of the human ear are remarkable. We can hear sounds that evoke mechanical vibrations of magnitudes comparable to those produced by thermal noise (de Vries 1948;Sivian and White 1933). Hearing is so sharply tuned to specific frequencies that trained musicians can distinguish tones differing in frequency by only 0.1% (Spiegel and Watson 1984). Finally, our ears can process sounds over a range of amplitudes encompassing six orders of magnitude, which corresponds to a trillionfold range in stimulus power (Knudsen 1923).These striking characteristics of our hearing emerge because the ear is not a passive sensory receptor, but possesses an active process that augments audition in three ways (reviewed in Hudspeth 2008;Manley 2000Manley , 2001. First, amplification renders hearing several hundred times as sensitive as would be expected for a passive system. The active process next exhibits tuning that sharpens our frequency discrimination. Finally, a compressive nonlinearity ensures that inputs spanning an enormous range of sound-pressure levels are systematically encoded by a modest range of mechanical vibrations and in turn of receptor potentials and nerve-fiber firing rates. The active process additionally exhibits the striking epiphenomenon of spontaneous otoacoustic emission, the production of sound by an ear in the absence of external stimulation. Although considerable attention has been devoted to these properties in mammalian and especially human hearing, the four defining features of the active process are equally characteristic of nonmammalian tetrapods (reviewed in Manley 2001).

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Prestin-based outer hair cell electromotility in knockin mice does not appear to adjust the operating point of a cilia-based amplifier

Cited by 36 publications

References 41 publications

The V499G/Y501H Mutation Impairs Fast Motor Kinetics of Prestin and Has Significance for Defining Functional Independence of Individual Prestin Subunits

The V499G/Y501H Mutation Impairs Fast Motor Kinetics of Prestin and Has Significance for Defining Functional Independence of Individual Prestin Subunits

Normal Hearing Sensitivity at Low to Middle Frequencies with ∼25% Prestin

A Critique of the Critical Cochlea: Hopf—a Bifurcation—Is Better Than None

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