Sensory processing of sound by inner hair cells of the cochlea

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).
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).