Role of Kir4.1 Channel in Auditory Function: Impact on Endocochlear Potential and Hearing Loss

Abstract

Hearing loss can result from impairments in structures that support endocochlear potential, as they play a crucial role in the transduction and transmission of auditory waves. This aspect has been the subject of several studies to date. In our review, the role of ion transport channels and pumps involved in hearing function has been highlighted, emphasizing how important the Kir4.1 channel is in maintaining the endocochlear potential. The Kir4.1 channel, a member of the inwardly rectifying potassium channel (Kir) family, plays a key role in the regulation of cell electrical activity and potassium ion homeostasis. The cochlear expression of these channels is at the level of the intermediate cells of the vascular stria, in the root cells of the outer sulcus, and in the glial cells of the spiral ganglion. In development, its expression demonstrates its involvement in the progression of pathologies related to potassium channel dysfunction, and its activation in the stria vascularis is directly related to the generation of endocochlear potential. Kir4.1 is fundamental in stabilizing the resting membrane potential of cells and modulating their excitability, as it facilitates a greater influx of potassium into cells compared to efflux when the membrane potential is negative. Mutations in the K+ channel gene KCNJ10 (Kir4.1) have been associated with several disorders, with the most significant studies on EAST/SeSAME syndrome and Pendred syndrome. Recent research has explored the metabolic importance of potassium channel changes associated with stria vascularis degeneration in the progression of age-related hearing loss. Furthermore, in ototoxicity studies, the Kir4.1 channel has been shown to have the ability to compensate for the deficiency of other K+ channels, as it maintains the cochlear homeostasis by correcting the imbalanced K+ concentration.