Sensory processing of sound by outer hair cells of the cochlea

Stable Identifier
R-HSA-9662361
Type
Pathway
Species
Homo sapiens
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser

Outer hair cells (OHCs) produce amplification of sound waves in the cochlea by shortening and lengthening in response to sound, a phenomenon called electromotility (reviewed in Kim and Fettiplace 2014, Fettiplace 2016, Fettiplace 2017, Fritzsch et al. 2017, Ashmore 2019). Like inner hair cells, OHCs possess apical stereocilia arranged in rows of ascending height. A taller stereocilium is connected to a shorter stereocilium by a tip link comprising a CDH23 dimer onthe side of the taller stereocilium and a PCDH15 dimer on theapex of the shorter stereocilium. PCDH15 interacts with LHFPL5, a subunit of the mechanoelectrical transduction channel complex (MET channel, also called the mechanotransduction channel), which contains TMC1 or TMC2, TMIE, CIB2, and LHFPL5 (reviewed in Fettiplace 2016). Deflection of the stereocilia in one direction produces tension on the tip link that increases the open probability of the MET channel, resulting in depolarization of the OHC. Deflection of the stereocilia in the opposite direction produces compression on the tip link that decreases the the open probability of the MET channel, resulting in hyperpolarization of the OHC.
Sound causes micromechanical motions of the organ of Corti that result in alternating tension and compression in the tip link that produce excitatory-inhibitory cycles of MET channel openings and closings relative to the MET channel's resting open probability. This causes directionally alternating fluxes of K+ and Ca2+, yielding depolarization-hyperpolarization cycles that cause conformational changes in prestin (SLC26A5). These cycles are asymmetrical, with contraction caused by depolarization dominating elongation caused by hyperpolarization due to the asymmetry of the open probability of MET channels. Stereociliary ATP2B2 (PMCA2) extrudes calcium ions and basally located KCNQ4 extrudes potassium ions to repolarize the OHC.
Depolarization of the OHC causes a decrease in length of the OHC due to a very rapid, voltage-sensitive change in conformation of the membrane protein prestin (SLC26A5), an unusual member of the anion transporter family located in the lateral membrane (Mahendrasingam et al, 2010) that appears to respond to cytosolic chloride by altering its conformation in the plane of the plasma membrane (reviewed in Dallos et al. 2006, Dallos 2008, Hudspeth 2014, Reichenbach and Hudspeth 2014, Ashmore 2019, Santos-Sacchi 2019). Prestin also appears to act as a weak chloride-bicarbonate antiporter (Mistrik et al. 2012). Changes in length of the OHCs cause movement of the reticular lamina toward and away from the basilar membrane.

Literature References
PubMed ID Title Journal Year
28484373 Evolution and Development of the Inner Ear Efferent System: Transforming a Motor Neuron Population to Connect to the Most Unusual Motor Protein via Ancient Nicotinic Receptors

Fritzsch, B, Elliott, KL

Front Cell Neurosci 2017
30747242 The speed limit of outer hair cell electromechanical activity

Santos-Sacchi, J

HNO 2019
27410728 Is TMC1 the Hair Cell Mechanotransducer Channel?

Fettiplace, R

Biophys. J. 2016
22890707 Mammalian prestin is a weak Cl⁻/HCO₃⁻ electrogenic antiporter

Mistrík, P, Daudet, N, Morandell, K, Ashmore, JF

J. Physiol. (Lond.) 2012
24987009 The physiology of mechanoelectrical transduction channels in hearing

Fettiplace, R, Kim, KX

Physiol. Rev. 2014
16873410 Prestin and the cochlear amplifier

Dallos, P, Zheng, J, Cheatham, MA

J. Physiol. (Lond.) 2006
28915323 Hair Cell Transduction, Tuning, and Synaptic Transmission in the Mammalian Cochlea

Fettiplace, R

Compr Physiol 2017
25096182 Integrating the active process of hair cells with cochlear function

Hudspeth, AJ

Nat. Rev. Neurosci. 2014
25006839 The physics of hearing: fluid mechanics and the active process of the inner ear

Reichenbach, T, Hudspeth, AJ

Rep Prog Phys 2014
18809494 Cochlear amplification, outer hair cells and prestin

Dallos, P

Curr. Opin. Neurobiol. 2008
20525072 The ultrastructural distribution of prestin in outer hair cells: a post-embedding immunogold investigation of low-frequency and high-frequency regions of the rat cochlea

Mahendrasingam, S, Beurg, M, Fettiplace, R, Hackney, CM

Eur. J. Neurosci. 2010
30181355 Outer Hair Cells and Electromotility

Ashmore, J

Cold Spring Harb Perspect Med 2019
Participants
Participates
Authored
Reviewed
Created
Cite Us!