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Sensory processing of sound by outer hair cells of the cochlea

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9662361

PubChem

R-HSA-9662361

Description

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.

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SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

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UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
A4UGR9	Xin actin-binding repeat-containing protein 2	CMYA3 XIRP2	view
O00159	Unconventional myosin-Ic	MYO1C	view
O14936	Peripheral plasma membrane protein CASK	CASK LIN2	view
P06396	Gelsolin	GSN	view
P15311	Ezrin	EZR VIL2	view
P26038	Moesin	MSN	view
P35241	Radixin	RDX	view
P35579	Myosin-9	MYH9	view
P58743	Prestin	PRES SLC26A5	view
P60709	Actin, cytoplasmic 1	ACTB	view

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