Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway
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INVITED REVIEW
Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway Barbara Peixoto Pinheiro 1 Youssef Adel 1
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Barbara Vona 1
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Hubert Löwenheim 1
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Lukas Rüttiger 2 & Marlies Knipper 2
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Received: 24 September 2020 / Revised: 27 October 2020 / Accepted: 10 November 2020 # The Author(s) 2020
Abstract Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly and constitutes the third highest risk factor for dementia. Lifetime noise exposure, genetic predispositions for degeneration, and metabolic stress are assumed to be the major causes of ARHL. Both noise-induced and hereditary progressive hearing have been linked to decreased cell surface expression and impaired conductance of the potassium ion channel KV7.4 (KCNQ4) in outer hair cells, inspiring future therapies to maintain or prevent the decline of potassium ion channel surface expression to reduce ARHL. In concert with KV7.4 in outer hair cells, KV7.1 (KCNQ1) in the stria vascularis, calcium-activated potassium channels BK (KCNMA1) and SK2 (KCNN2) in hair cells and efferent fiber synapses, and KV3.1 (KCNC1) in the spiral ganglia and ascending auditory circuits share an upregulated expression or subcellular targeting during final differentiation at hearing onset. They also share a distinctive fragility for noise exposure and age-dependent shortfalls in energy supply required for sustained surface expression. Here, we review and discuss the possible contribution of select potassium ion channels in the cochlea and auditory pathway to ARHL. We postulate genes, proteins, or modulators that contribute to sustained ion currents or proper surface expressions of potassium channels under challenging conditions as key for future therapies of ARHL. Keywords Kv7.4 . Kv7.1 . BK . SK2 . Kv3.1 . Presbycusis
Introduction Age-related hearing loss (ARHL), or presbycusis, is the most prevalent sensory deficit in the elderly [1]. Although it is not lifethreatening, this condition is associated with significant psychological and medical morbidity, including social isolation, frailty, depression, and cognitive decline [2–5]. As a major risk factor for dementia [6], the prevention of hearing loss with age has
This article is part of the special issue on Aging Brain in Pflügers Archiv—European Journal of Physiology * Marlies Knipper [email protected] 1
Translational Hearing Research, Tübingen Hearing Research Center, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, 72076 Tübingen, Germany
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Molecular Physiology of Hearing, Tübingen Hearing Research Center, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, 72076 Tübingen, Germany
been recently suggested as a foremost modifying factor to lower future dementia prevalence [7]. ARHL occurs in most mammals with variations in the age of onset, rate of decline, and magnitude of degeneration in the cochlea and the auditory pathway [8–11]. The affected cochlear structures include the stria
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