Pathway
Sensory processing of sound by inner hair cells of the cochlea
Inner hair cells (IHCs) of the cochlea transduce sound waves into an ionic (mainly potassium) current that leads to exocytosis of glutamate from the IHC and activation of postsynaptic type I afferent fibers of the radial ganglion (reviewed in Meyer and Moser 2010, Moser and Vogl 2016, Fettiplace 2017). IHCs have stereocilia on their apical surface that are arranged in rows of increasing height, a "staircase" arrangement. Stereocilia of different rows are connected by a tip link comprising a CDH23 dimer on the taller stereocilium bound to a PCDH15 dimer on the shorter stereocilium. PCDH15 interacts with LHFPL5, an auxiliary subunit of the mechanoelectrical transduction channel (MET channel, also called the mechanotransduction channel), which contains at least TMC1 (adults) or TMC2 (newborns), TMIE, and the auxiliary subunits LHFPL5 and CIB2 (reviewed in Fettiplace and Kim 2014, Fettiplace 2016).
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Deflection of the stereocilia by sound waves creates tension on the tip link that increases the open probability of the MET channel, which then transports calcium and potassium ions from the scala media into the IHC, depolarizing the IHC (reviewed in Fettiplace 2017). The potassium channel KCNQ4 located in the neck region of the cell may also participate in depolarization. The depolarization of the IHC opens voltage-gated Cav1.3 channels (CACNA1D:CACA2D2:CACNB2) located in stripes near ribbon synapses on the basolateral surface of the IHC. The resulting localized influx of calcium ions activates exocytosis of glutamate into the synapse by an interaction between calcium and Otoferlin (OTOF) on glutamate-loaded vesicles in the IHC (reviewed in Wichmann 2015).
Ribbon synapses are characterized by a multiprotein complex, the ribbon, that contains at least BASSOON, RIBEYE (an isoform of CTBP2), and PICCOLINO (a small isoform of PICCOLO) and appears to act to transiently tether vesicles near the synapse and thereby increase the pool of readily releasable vesicles (reviewed in Safieddine et al. 2012, Wichman and Moser 2015, Pangrsic and Vogl 2018, Moser et al. 2020).
ATP2B1 calcium channels, ATP2B2 calcium channels, KCNMA1:KCNMB1:LRRC52 potassium channels, and basolateral KCNQ4 potassium channels transport cations out of the IHC and thereby act to repolarize the cell and limit the duration of the synaptic potentials (reviewed in Patuzzi 2011, Oak and Yi 2014).
What the reference databases state
Statements
66 statements
66 statements · 1 reference database · Subject: Sensory processing of sound by inner hair cells of the cochlea · Sources: Reactome
- ACTB participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- ACTG1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- ATP2B1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- BSN participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- CABP1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- CABP2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- CACNA1D participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- CACNA2D2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- CACNB2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- CAPZA1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- CAPZA2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- CAPZB participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
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- CASK participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- CDH23 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- CIB2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- CLIC5 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- DNAJC5 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- EPB41L1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- EPB41L3 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- EPS8 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- EPS8L2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- ESPN participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- ESPNL participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- EZR participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- FSCN2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- GRXCR1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- GRXCR2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- KCNMA1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- KCNMB1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- KCNQ4 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- LHFPL5 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- LRRC52 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- MSN participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- MYH9 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- MYO15A participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- MYO1C participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- MYO3A participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- MYO3B participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- MYO7A participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- OTOF participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- PCDH15 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- PCLO participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- PJVK participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- PLS1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- RAB3A participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- RDX participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- RIPOR2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- SLC17A8 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- SNAP25 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- SPTAN1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- SPTBN1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- STRC participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- STX1A participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- SYN1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- SYP participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- TMC1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- TMC2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- TMIE participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- TPRN participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- TWF1 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- TWF2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- USH1C participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- USH1G participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- VAMP2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- WHRN participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only
- XIRP2 participates in Sensory processing of sound by inner hair cells of the cochleaProteinReactome R-HSA-9662360Inferred only