Recent advances in cochlear hair cell nanophysiology: subcellular compartmentalization of electrical signaling in compact sensory cells

Abstract

In recent years, genetics, physiology, and structural biology have advanced into the molecular details of the sensory physiology of auditory hair cells. Inner hair cells (IHCs) and outer hair cells (OHCs) mediate two key functions: active amplification and non-linear compression of cochlear vibrations by OHCs and sound encoding by IHCs at their afferent synapses with the spiral ganglion neurons. OHCs and IHCs share some molecular physiology, e.g. mechanotransduction at the apical hair bundles, ribbon-type presynaptic active zones, and ionic conductances in the basolateral membrane. Unique features enabling their specific function include prestin-based electromotility of OHCs and indefatigable transmitter release at the highest known rates by ribbon-type IHC active zones. Despite their compact morphology, the molecular machineries that either generate electrical signals or are driven by these signals are essentially all segregated into local subcellular structures. This review provides a brief account on recent insights into the molecular physiology of cochlear hair cells with a specific focus on organization into membrane domains.

Potential Mechanisms of Hearing Loss Due to Impaired Potassium Circulation in the Organ of Corti

“…When sound waves enter the cochlea, their vibrations are transmitted through the perilymph of the scala tympani to the basilar membrane, causing the HCs to bend their stereocilia against the tectorial membrane. As explained previously, this movement opens the mechanosensitive channels located on the stereocilia of the HCs, activating K + influx [6,16]. The RPs trigger the release of the neurotransmitter glutamate by the IHCs, while activating the amplification process in the OHCs [43].…”

“…Vesicle release in IHCs occurs in the basolateral membrane, which contains the active zones characterized by the presence of synaptic ribbons that supply ultrafast and precise synaptic vesicles for exocytosis, to release glutamate into the synaptic cleft (Figure 2, left) [43,44]. The released neurotransmitters then stimulate postsynaptic afferent nerve fibers from the SG neurons, sending electrical signals to the brain for sound interpretation through the auditory pathway [16,45]. The primary function of OHCs is to amplify and fine-tune the sound signals before they reach the IHCs.…”

“…After sound perception, K + leaves the HCs and returns to the stria vascularis through gap junctions (GJs) and transporters present in the surrounding SCs. The flow and recycling of K + ions play a vital role in the conversion of sound vibrations into electrical signals that can be transmitted to the brain for auditory perception [14][15][16][17][18][19][20][21][22].…”

Is there an unmet medical need for improved hearing restoration?

“…Specifically, high frequencies most effectively vibrate the membrane at the cochlear base where it is narrow and stiff, while low‐frequency waves vibrate maximally the softest and widest area of the membrane at the cochlear apex. This way, this micromechanical spectral analyzer establishes a frequency map in the cochlea (also known as the tonotopic axis; Kandel et al , 2012 ) that is read out by mechanosensory inner and outer hair cells (IHCs and OHCs) (Fettiplace, 2017 ; Effertz et al , 2020 ).…”

“…IHCs form one and OHCs three rows in the organ of Corti running along the entire length of the basilar membrane. Both carry hair bundles at their apex as the mechanoelectrical transduction machinery: Deflection of the bundle opens mechanotransducer channels, which enables depolarizing cation—mostly potassium—influx into the hair cell (Hudspeth, 2014 ; Fettiplace, 2017 ; Effertz et al , 2020 ). Hair bundles of OHCs are mechanically connected to the tectorial membrane that lies above the organ of Corti.…”