Pathway
Sensory processing of sound by outer hair cells of the cochlea
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.
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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 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. Changes in length of the OHCs cause movement of the reticular lamina toward and away from the basilar membrane.
What the reference databases state
Statements
53 statements
53 statements · 1 reference database · Subject: Sensory processing of sound by outer hair cells of the cochlea · Sources: Reactome
- ACTB participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- ACTG1 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- CASK participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- CDH23 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- CHRNA10 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- CHRNA9 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- CIB2 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- CLIC5 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- EPB41L1 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- EPB41L3 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- EPS8 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- EPS8L2 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
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- ESPN participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- ESPNL participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- EZR participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- FSCN2 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- GRXCR1 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- GRXCR2 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- GSN participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- KCNMA1 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- KCNMB1 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- KCNN2 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- KCNQ4 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- LHFPL5 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- MPP1 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- MSN participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- MYH9 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- MYO15A participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- MYO1C participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- MYO3A participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- MYO3B participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- MYO7A participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- OTOG participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- OTOGL participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- PCDH15 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- PJVK participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- PLS1 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- RDX participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- RIPOR2 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- SLC26A5 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- SPTAN1 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- SPTBN1 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- STRC participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- TMC1 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- TMC2 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- TMIE participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- TPRN participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- TWF1 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- TWF2 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- USH1C participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- USH1G participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- WHRN participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only
- XIRP2 participates in Sensory processing of sound by outer hair cells of the cochleaProteinReactome R-HSA-9662361Inferred only