Indispensable Role of Ion Channels and Transporters in the Auditory System

Abstract

Ear is a complex system where appropriate ionic composition is essential for maintaining the tissue homeostasis and hearing function. Ion transporters and channels present in the auditory system plays a crucial role in maintaining proper ionic composition in the ear. The extracellular fluid, called endolymph, found in the cochlea of the mammalian inner ear is particularly unique due to its electrochemical properties. At an endocochlear potential of about +80 mV, signaling initiated by acoustic stimuli at the level of the hair cells is dependent on the unusually high potassium (K ) concentration of endolymph. There are ion channels and transporters that exists in the ear to ensure that K is continually being cycled into the stria media endolymph. This review is focused on the discussion of the molecular and genetic basis of previously and newly recognized ion channels and transporters that support sensory hair cell excitation based on recent knock-in and knock-out studies of these channels. This article also addresses the molecular and genetic defects and the pathophysiology behind Meniere's disease as well as how the dysregulation of these ion transporters can result in severe defects in hearing or even deafness. Understanding the role of ion channels and transporters in the auditory system will facilitate in designing effective treatment modalities against ear disorders including Meniere's disease and hearing loss. J. Cell. Physiol. 232: 743-758, 2017. © 2016 Wiley Periodicals, Inc.

Recent advances in understanding the pathogenesis and management of reticular dysgenesis

“…Most models for the maintenance of these high potassium concentrations include a potassium circuitry driven by transporters and ion channels from the hair cells to the supporting cells to the spiral ligament and eventually back to the SV, where potassium is secreted back into the scala media endolymph (Mittal et al , ).…”

“…Gly100Asp (1) del5kb (6) Gly47Arg (1) Glu9*(2) Met1Leu(2) Met1Val(5) Cys40Valfs*5(1) Gly205Aspfs*92 (2) Asp165Gly (4) Arg186Cys (3) Exon4-1G>A (2) Leu134Alafs*32(1) Pro158Leufs*6(2) 45 74 141 178 30 22 transporters and ion channels from the hair cells to the supporting cells to the spiral ligament and eventually back to the SV, where potassium is secreted back into the scala media endolymph (Mittal et al, 2017).…”

Recent Advancements in the Regeneration of Auditory Hair Cells and Hearing Restoration

“…Adenoviral vectors containing genes for wild-type GFP and potassium channel protein KCNQ4 were applied to the sensory epithelia. KCNQ4 is known to cause dominant-progressive hearing loss when mutated (Kubisch et al, 1999; Mittal et al, 2017). Strong expression of an exogenous transgene (GFP) in hair cells and supporting cells was observed, indicating that the adenovirus transfection can drive the expression of a wild-type form of human deafness genes, e.g., KCNQ4.…”

“…The complexity of the auditory system is what makes hearing particularly vulnerable to damage (Moser and Starr, 2016; Mittal et al, 2017). Sound transduction begins at the pinna, which is responsible for the collection and funneling of sound-waves into the auditory canal (Yan and Liu, 2008).…”

“…The contraction of these muscles is vital for preventing mechanical damage and stimulus-induced hearing loss. Failure in any of the elements of the hearing pathway, including the tensor tympani and stapedius muscles, may result in hearing loss (Yan and Liu, 2008; Géléoc and Holt, 2014; Moser and Starr, 2016; Mittal et al, 2017). …”