Skip to main content
SpringerLink
Log in

The Remarkable Outer Hair Cell: Proceedings of a Symposium in Honour of W. E. Brownell

  • Review
  • Published:
Journal of the Association for Research in Otolaryngology Aims and scope Submit manuscript

Abstract

In 1985, Bill Brownell and colleagues published the remarkable observation that cochlear outer hair cells (OHCs) express voltage-driven mechanical motion: electromotility. They proposed OHC electromotility as the mechanism for the elusive “cochlear amplifier” required to explain the sensitivity of mammalian hearing. The finding and hypothesis stimulated an explosion of experiments that have transformed our understanding of cochlear mechanics and physiology, the evolution of hair cell structure and function, and audiology. Here, we bring together examples of current research that illustrate the continuing impact of the discovery of OHC electromotility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Notes

  1. One could say that we take seriously the title of this symposium: “The Remarkable Outer Hair Cell,” with an emphasis on the The, as if there were only one. Not literally one, of course, as Wheeler and Feynman proposed for the electron, but rather a uniform array with no particular spatial gradient in biophysical response properties other than those arising from–or contributing to–the cochlear map.

References

  • Abdala C, Kalluri R (2017) Towards a joint reflection-distortion otoacoustic emission profile: Results in normal and impaired ears. J Acoust Soc Am 142:812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Altoè A, Shera CA (2020a) The cochlear ear horn: geometric origin of tonotopic variations in auditory signal processing. Sci Rep 10:20528

    Article  PubMed  PubMed Central  Google Scholar 

  • Altoè A, Shera CA (2020b) Nonlinear cochlear mechanics without direct vibration-amplification feedback. Phys Rev Res 2:013218

  • Ashmore J (2008) Cochlear outer hair cell motility. Physiological Reviews 88(1):173–210

    Article  CAS  PubMed  Google Scholar 

  • Ashmore JF (1987) A fast motile response in guinea-pig outer hair cells: the cellular basis of the cochlear amplifier. J Physiol 388:323–347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ballestero J, de San Z, Martin J, Goutman J, Elgoyhen AB, Fuchs PA, Katz E (2011) Short-term synaptic plasticity regulates the level of olivocochlear inhibition to auditory hair cells. J Neurosci 31:14763–14774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bavi N, Clark MD, Contreras GF, Shen R, Reddy BG et al (2021) The conformational cycle of prestin underlies outer-hair cell electromotility. Nature 600(7889):553–558

  • Boffi JC, Marcovich I, Gill-Thind JK, Corradi J, Collins T et al (2017) Differential contribution of subunit interfaces to alpha9alpha10 nicotinic acetylcholine receptor function. Mol Pharmacol 91:250–262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brownell WE, Bader CR, Bertrand D, de Ribaupierre Y (1985) Evoked mechanical responses of isolated cochlear outer hair cells. Science 227:194–196

    Article  CAS  PubMed  Google Scholar 

  • Butan C, Song Q, Bai J, Tan W, Navaratnam D, Santos-Sacchi J (2022) Single particle cryo-EM structure of the outer hair cell motor protein prestin. Nat Commun 13(1):290

  • Carney LH, McDuffy MJ, Shekhter I (1999) Frequency glides in the impulse responses of auditory-nerve fibers. J Acoust Soc Am 105:2384–2391

    Article  CAS  PubMed  Google Scholar 

  • Cedolin L, Delgutte B (2005) Pitch of complex tones: rate-place and interspike interval representations in the auditory nerve. J Neurophysiol 94:347–362

    Article  PubMed  Google Scholar 

  • Cortese M, Papal S, Pisciottano F, Elgoyhen AB, Hardelin JP et al (2017) Spectrin betaV adaptive mutations and changes in subcellular location correlate with emergence of hair cell electromotility in mammalians. Proc Natl Acad Sci USA 114:2054–2059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dallos P (2008) Cochlear amplification, outer hair cells and prestin. Curr Opin Neurobiol 18:370–376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dallos P, Zheng J, Cheatham MA (2006) Prestin and the cochlear amplifier. J Physiol 576(Pt1):37–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Boer E (1983) On active and passive cochlear models—Toward a generalized analysis. J Acous Soc Am 73(2):574–576

  • Dent JA (2006) Evidence for a diverse Cys-loop ligand-gated ion channel superfamily in early bilateria. J Mol Evol 62:523–535

    Article  CAS  PubMed  Google Scholar 

  • Dewey JB, Altoè A, Shera CA, Applegate BE, Oghalai JS (2021) Cochlear outer hair cell electromotility enhances organ of Corti motion on a cycle-by-cycle basis at high frequencies in vivo. Proc Natl Acad Sci USA 118(43):e2025206118

  • Dewey JB, Applegate BE, Oghalai JS (2019) Amplification and suppression of traveling waves along the mouse organ of Corti: evidence for spatial variation in the longitudinal coupling of outer hair cell-generated forces. J Neurosci 39:1805–1816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elgoyhen AB, Franchini LF (2011) Prestin and the cholinergic receptor of hair cells: positively-selected proteins in mammals. Hear Res 273:100–108

    Article  CAS  PubMed  Google Scholar 

  • Elgoyhen AB, Johnson DS, Boulter J, Vetter DE, Heinemann S (1994) a9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells. Cell 79:705–715

    Article  CAS  PubMed  Google Scholar 

  • Elgoyhen AB, Katz E (2012) The efferent medial olivocochlear-hair cell synapse. J Physiol Paris 106:47–56

    Article  PubMed  Google Scholar 

  • Elgoyhen AB, Vetter D, Katz E, Rothlin C, Heinemann S, Boulter J (2001) Alpha 10: a determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells. Proc Natl Acad Sci USA 98:3501–3506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fallah E, Strimbu CE, Olson ES (2019) Nonlinearity and amplification in cochlear responses to single and multi-tone stimuli. Hear Res 377:271–281

    Article  PubMed  PubMed Central  Google Scholar 

  • Fettiplace R (2020) Diverse mechanisms of sound frequency discrimination in the vertebrate cochlea. Trends Neurosci 43(2):88–102 

  • Franchini LF, Elgoyhen AB (2006) Adaptive evolution in mammalian proteins involved in cochlear outer hair cell electromotility. Mol Phylogenet Evol 41:622–635

    Article  CAS  PubMed  Google Scholar 

  • Frank G, Hemmert W, Gummer AW (1999) Limiting dynamics of high-frequency electromechanical transduction of outer hair cells. Proc Natl Acad Sci USA 96:4420–4425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao SS, Wang R, Raphael PD, Moayedi Y, Groves AK et al (2014) Vibration of the organ of Corti within the cochlear apex in mice. J Neurophysiol 112:1192–1204

    Article  PubMed  PubMed Central  Google Scholar 

  • Ge J, Elferich J, Dehghani-Ghahnaviyeh S, Zhao Z, Meadows M et al (2021) Molecular mechanism of prestin electromotive signal amplification. Cell 184(4669–79):e13

    Google Scholar 

  • Geertsma ER, Chang YN, Shaik FR, Neldner Y, Pardon E et al (2015) Structure of a prokaryotic fumarate transporter reveals the architecture of the SLC26 family. Nat Struct Mol Biol 22:803–808

    Article  CAS  PubMed  Google Scholar 

  • Gold T (1948) Hearing. II. The physical basis of the action of the cochlea. Proc Roy Soc London B 135:492–498

    Google Scholar 

  • Gomez-Casati ME, Fuchs PA, Elgoyhen AB, Katz E (2005) Biophysical and pharmacological characterization of nicotinic cholinergic receptors in cochlear inner hair cells. J Physiol 566:103–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Housley GD, Ashmore JF (1992) Ionic currents of outer hair cells isolated from the guinea-pig cochlea. J Physiol 448:73–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hubbard AE, Mountain DC (1983) Alternating current delivered into the scala media alters sound pressure at the eardrum. Science 222:510–512

    Article  CAS  PubMed  Google Scholar 

  • Iwasa KH (2017) Negative membrane capacitance of outer hair cells: electromechanical coupling near resonance. Sci Rep 7:12118

    Article  PubMed  PubMed Central  Google Scholar 

  • Johnson SL, Beurg M, Marcotti W, Fettiplace R (2011) Prestin-driven cochlear amplification is not limited by the outer hair cell membrane time constant. Neuron 70:1143–1154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kemp DT (1978) Stimulated acoustic emissions from within the human auditory system. J Acoust Soc Am 64:1386–1391

    Article  CAS  PubMed  Google Scholar 

  • Khanna SM, Leonard DG (1982) Basilar membrane tuning in the cat cochlea. Science 215:305–306

    Article  CAS  PubMed  Google Scholar 

  • Kim DO, Molnar CE, Pfeiffer RR (1973) A system of nonlinear differential equations modeling basilar-membrane motion. J Acoust Soc Am 54:1517–1529

    Article  CAS  PubMed  Google Scholar 

  • Koppl C (2011) Birds - same thing, but different? Convergent evolution in the avian and mammalian auditory systems provides informative comparative models. Hear Res 273:65–71

    Article  PubMed  Google Scholar 

  • Lee HY, Raphael PD, Park J, Ellerbee AK, Applegate BE, Oghalai JS (2015) Noninvasive in vivo imaging reveals differences between tectorial membrane and basilar membrane traveling waves in the mouse cochlea. Proc Natl Acad Sci USA 112:3128–3133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lipovsek M, Fierro A, Perez EG, Boffi JC, Millar NS et al (2014) Tracking the molecular evolution of calcium permeability in a nicotinic acetylcholine receptor. Mol Biol Evol 31:3250–3265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lipovsek M, Im GJ, Franchini LF, Pisciottano F, Katz E et al (2012) Phylogenetic differences in calcium permeability of the auditory hair cell cholinergic nicotinic receptor. Proc Natl Acad Sci USA 109:4308–4313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mammano F, Ashmore JF (1996) Differential expression of outer hair cell potassium currents in the isolated cochlea of the guinea-pig. J Physiol 496(Pt 3):639–646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manley GA (2000) Cochlear mechanisms from a phylogenetic viewpoint. Proc Natl Acad Sci USA 97:11736–11743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manley GA (2017) The mammalian Cretaceous cochlear revolution. Hear Res 352:23–29

    Article  PubMed  Google Scholar 

  • Marcovich I, Moglie MJ, Carpaneto Freixas AE, Trigila AP, Franchini LF et al (2020) Distinct evolutionary trajectories of neuronal and hair cell nicotinic acetylcholine receptors. Mol Biol Evol 37:1070–1089

    Article  CAS  PubMed  Google Scholar 

  • Mistrik P, Daudet N, Morandell K, Ashmore JF (2012) Mammalian prestin is a weak Cl(-)/HCO(3)(-) electrogenic antiporter. J Physiol 590:5597–5610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neely ST, Kim DO (1983) An active cochlear model showing sharp tuning and high sensitivity. Hear Res 9(2):123–130

  • Olson ES, Strimbu CE (2020) Cochlear mechanics: new insights from vibrometry and Optical Coherence Tomography. Curr Opin Physiol 18:56–62

    Article  PubMed  PubMed Central  Google Scholar 

  • Pisciottano F, Cinalli AR, Stopiello JM, Castagna VC, Elgoyhen AB et al (2019) Inner ear genes underwent positive selection and adaptation in the mammalian lineage. Mol Biol Evol 36:1653–1670

    Article  CAS  PubMed  Google Scholar 

  • Puria S, Allen JB (1991) A parametric study of cochlear input impedance. J Acoust Soc Am 89:287–309

    Article  CAS  PubMed  Google Scholar 

  • Rabbitt RD (2020) The cochlear outer hair cell speed paradox. Proc Natl Acad Sci USA 117:21880–21888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rhode WS (1971) Observations of the vibration of the basilar membrane in squirrel monkeys using the Mössbauer technique. J Acoust Soc Am 49: Suppl 2:1218

  • Rothlin C, Verbitsky M, Katz E, Elgoyhen A (1999) The a9 nicotinic acetylcholine receptor shares pharmacological properties with type A g-aminobutyric acid, glycine and type 3 serotonin receptors. Molec Pharmacol 55:248–254

    Article  CAS  Google Scholar 

  • Rothlin CV, Lioudyno MI, Silbering AF, Plazas PV, Casati ME et al (2003) Direct interaction of serotonin type 3 receptor ligands with recombinant and native alpha 9 alpha 10-containing nicotinic cholinergic receptors. Mol Pharmacol 63:1067–1074

    Article  CAS  PubMed  Google Scholar 

  • Santos-Sacchi J, Iwasa KH, Tan W (2019) Outer hair cell electromotility is low-pass filtered relative to the molecular conformational changes that produce nonlinear capacitance. J Gen Physiol 151:1369–1385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santos-Sacchi J, Tan W (2018) The frequency response of outer hair cell voltage-dependent motility is limited by kinetics of prestin. J Neurosci 38:5495–5506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santos-Sacchi J, Tan W (2020) Complex nonlinear capacitance in outer hair cell macro-patches: effects of membrane tension. Sci Rep 10:6222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasmal A, Grosh K (2019) Unified cochlear model for low- and high-frequency mammalian hearing. Proc Natl Acad Sci USA 116:13983–13988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sgard F, Charpentier E, Bertrand S, Walker N, Caput D et al (2002) A novel human nicotinic receptor subunit, a10, that confers functionality to the a9-subunit. Molec Pharmacol 61:150–159

    Article  CAS  Google Scholar 

  • Shera CA (2001) Frequency glides in click responses of the basilar membrane and auditory nerve: their scaling behavior and origin in traveling-wave dispersion. J Acoust Soc Am 109:2023–2034

    Article  CAS  PubMed  Google Scholar 

  • Shera CA, Guinan JJ Jr (1999) Evoked otoacoustic emissions arise by two fundamentally different mechanisms: a taxonomy for mammalian OAEs. J Acoust Soc Am 105:782–798

    Article  CAS  PubMed  Google Scholar 

  • Shera CA, Guinan JJ Jr, Oxenham AJ (2010) Otoacoustic estimation of cochlear tuning: validation in the chinchilla. J Assoc Res Otolaryngol 11:343–365

    Article  PubMed  PubMed Central  Google Scholar 

  • Shera CA, Tubis A, Talmadge CL (2005) Coherent reflection in a two-dimensional cochlea: short-wave versus long-wave scattering in the generation of reflection-source otoacoustic emissions. J Acoust Soc Am 118:287–313

    Article  PubMed  Google Scholar 

  • Shera CA, Zweig G (1991) A symmetry suppresses the cochlear catastrophe. J Acoust Soc Am 89:1276–1289

    Article  CAS  PubMed  Google Scholar 

  • Sienknecht UJ, Köppl C, Fritzsch B (2014) Evolution and development of hair cell polarity and efferent function in the inner ear. Brain Behav Evol 83:150–161

    Article  PubMed  Google Scholar 

  • Strimbu CE, Wang Y, Olson ES (2020) Manipulation of the endocochlear potential reveals two distinct types of cochlear nonlinearity. Biophys J 119:2087–2101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tobin M, Chaiyasitdhi A, Michel V, Michalski N, Martin P (2019) Stiffness and tension gradients of the hair cell's tip-link complex in the mammalian cochlea. Elife 8:e43473

  • Vavakou A, Cooper NP, van der Heijden M (2019) The frequency limit of outer hair cell motility measured in vivo. Elife 8:e47667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  •  Vater M, Kössl, M (2011) Comparative aspects of cochlear functional organization in mammals. Hear Res 273(1-2):89–99

  • Verbitsky M, Rothlin C, Katz E, Elgoyhen AB (2000) Mixed nicotinic-muscarinic properties of the a9 nicotinic cholinergic receptor. Neuropharmacology 39:2515–2524

    Article  CAS  PubMed  Google Scholar 

  • Walter JD, Sawicka M, Dutzler R (2019) Cryo-EM structures and functional characterization of murine Slc26a9 reveal mechanism of uncoupled chloride transport. Elife 8:e46986

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Fallah E, Olson ES (2019) Adaptation of cochlear amplification to low endocochlear potential. Biophys J 116:1769–1786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng J, Shen W, He DZ, Long KB, Madison LD, Dallos P (2000) Prestin is the motor protein of cochlear outer hair cells. Nature 405:149–155

    Article  CAS  PubMed  Google Scholar 

  • Zweig G, Shera CA (1995) The origin of periodicity in the spectrum of evoked otoacoustic emissions. J Acoust Soc Am 98:2018–2047

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

J. S. Oghalai and J. B. Dewey: Caruso Dept. of Otolaryngology and NIH/NIDCD Grants R01 DC014450, DC013774, and DC017741 to J.S.O., and NIH/NIDCD Grants F32 DC016211 and R21 DC019209 to J.B.D. E. S. Olson, C. E. Strimbu, and Y. Wang: NIH/NIDCD Grant R01 DC015362. C. A. Shera and A. Altoè: Caruso Dept. of Otolaryngology and NIH/NIDCD Grants R01 DC003687. C. Abdala: NIH/NIDCD Grants R01 DC003552 and R01 DC003687. A. B. Elgoyen: NIH/NIDCD Grant R01 DC001508. R. A. Eatock: NIH/NIDCD Grant R01 DC012347. R. M. Raphael: NIH/NIDCD Grant R01 DC012347.

Author information

Authors and Affiliations

  1. UCL Ear Institute, University College London, London, UK

    Jonathan F. Ashmore

  2. Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, USA

    John S. Oghalai & James B. Dewey

  3. Department of Otolaryngology Head and Neck Surgery, Vagelos College of Physicians and Surgeons, Columbia University, New York City, USA

    Elizabeth S. Olson, Clark E. Strimbu & Yi Wang

  4. Caruso Department of Otolaryngology and Department of Physics and Astronomy, University of Southern California, Los Angeles, USA

    Christopher A. Shera & Alessandro Altoè

  5. Caruso Department of Otolaryngology, University of Southern California, Los Angeles, USA

    Carolina Abdala

  6. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina

    Ana B. Elgoyhen

  7. Department of Neurobiology, University of Chicago, Chicago, USA

    Ruth Anne Eatock

  8. Department of Bioengineering, Rice University, Houston, USA

    Robert M. Raphael

Authors
  1. Jonathan F. Ashmore
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John S. Oghalai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James B. Dewey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elizabeth S. Olson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Clark E. Strimbu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christopher A. Shera
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alessandro Altoè
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Carolina Abdala
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ana B. Elgoyhen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ruth Anne Eatock
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Robert M. Raphael
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert M. Raphael.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ashmore, J.F., Oghalai, J.S., Dewey, J.B. et al. The Remarkable Outer Hair Cell: Proceedings of a Symposium in Honour of W. E. Brownell. JARO 24, 117–127 (2023). https://doi.org/10.1007/s10162-022-00852-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10162-022-00852-4

Keywords

Search

Navigation