Sensory processing of sound by inner hair cells of the cochlea

Stable Identifier
Homo sapiens
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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).
Literature References
PubMed ID Title Journal Year
26188105 Molecularly and structurally distinct synapses mediate reliable encoding and processing of auditory information

Wichmann, C

Hear. Res. 2015
27635230 New insights into cochlear sound encoding

Moser, T, Vogl, C

F1000Res 2016
27410728 Is TMC1 the Hair Cell Mechanotransducer Channel?

Fettiplace, R

Biophys. J. 2016
24925343 Voltage-gated K(+) channels contributing to temporal precision at the inner hair cell-auditory afferent nerve fiber synapses in the mammalian cochlea

Oak, MH, Yi, E

Arch. Pharm. Res. 2014
24987009 The physiology of mechanoelectrical transduction channels in hearing

Kim, KX, Fettiplace, R

Physiol. Rev. 2014
30251250 Balancing presynaptic release and endocytic membrane retrieval at hair cell ribbon synapses

Pangršič, T, Vogl, C

FEBS Lett. 2018
25874597 Relating structure and function of inner hair cell ribbon synapses

Wichmann, C, Moser, T

Cell Tissue Res. 2015
28915323 Hair Cell Transduction, Tuning, and Synaptic Transmission in the Mammalian Cochlea

Fettiplace, R

Compr Physiol 2017
31373863 Sensory Processing at Ribbon Synapses in the Retina and the Cochlea

Moser, T, Schmitz, F, Grabner, CP

Physiol. Rev. 2020
22715884 The auditory hair cell ribbon synapse: from assembly to function

Petit, C, Safieddine, S, El-Amraoui, A

Annu. Rev. Neurosci. 2012
21536120 Ion flow in cochlear hair cells and the regulation of hearing sensitivity

Patuzzi, R

Hear. Res. 2011
20802334 Structure and function of cochlear afferent innervation

Moser, T, Meyer, AC

Curr Opin Otolaryngol Head Neck Surg 2010
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