Roles of Key Ion Channels and Transport Proteins in Age-Related Hearing Loss

Abstract

The auditory system is a fascinating sensory organ that overall, converts sound signals to electrical signals of the nervous system. Initially, sound energy is converted to mechanical energy via amplification processes in the middle ear, followed by transduction of mechanical movements of the oval window into electrochemical signals in the cochlear hair cells, and finally, neural signals travel to the central auditory system, via the auditory division of the 8th cranial nerve. The majority of people above 60 years have some form of age-related hearing loss, also known as presbycusis. However, the biological mechanisms of presbycusis are complex and not yet fully delineated. In the present article, we highlight ion channels and transport proteins, which are integral for the proper functioning of the auditory system, facilitating the diffusion of various ions across auditory structures for signal transduction and processing. Like most other physiological systems, hearing abilities decline with age, hence, it is imperative to fully understand inner ear aging changes, so ion channel functions should be further investigated in the aging cochlea. In this review article, we discuss key various ion channels in the auditory system and how their functions change with age. Understanding the roles of ion channels in auditory processing could enhance the development of potential biotherapies for age-related hearing loss.

Cochlear Inflammaging in Relation to Ion Channels and Mitochondrial Functions

“…For instance, Schulte and Schmiedt [60] found that EP levels decrease first in the apex of the cochlea before decreasing in other regions of the cochlea as aging occurs, which is correlated with the expression levels of Na,K-ATPase found in the stria. Na,K-ATPase is important for ion transport, and there is a decrease in its presence with age in the stria [63], where its expression was found to be reduced up to 80% in aged CBA/CaJ mice [48,53]. Moreover, localization of decreasing Na,K-ATPase expression was seen to occur in the same regions where EP levels dropped [63].…”

“…More specifically, ion channel dysfunction in the auditory system has been shown to negatively impact hearing by mainly impacting the K + channels that affect the generation of the EP needed for hair cell depolarization. Here, age-related hearing disorders are often linked to a decrease in EP and reduction in K + channel functionality; reductions which while yet unconfirmed, can reasonably be attributed to inflammation and mitochondrial dysfunction [48].…”

“…Strial, or metabolic, presbycusis is the degradation of the SV. The SV is responsible for the generation of the endocochlear potential (EP) and maintaining the high potassium ion (K + ) content of the endolymph [48][49][50][51]. This is key for the normal signal transduction of sound information into the electrochemical responses of hair cells (HCs), which synapse on auditory nerve fibers to carry sound information to the brain.…”

“…NKCC1 is another key channel in the inner ear and it declines with aging. [48,[110][111][112]. Lui and coworkers showed progressive aging declines in NKCC1 protein and gene expressions in C57BL/6J mice [112].…”

“…Apart from ion transporters such as Na,K-ATPase and NKCC1, K + channels are involved in cochlear ion transport [48,50,62,[133][134][135][136]. Amongst the more than 100 potassium channels which have been identified, three inner ear K + channels-inwardly rectifying K + channels (Kir), voltage-activated K + channels (Kv), and calcium-activated K + channels (BKCa)-have been linked to inflammatory processes [137,138].…”