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.
Highlights
Age-related hearing loss (ARHL), or presbycusis, is the most prevalent sensory deficit in the elderly [1]
We discuss the following K+ channels with functional expression during or after hearing onset, that is, around postnatal day (P) 12 in rodents, and around embryonic week (EW) 27 in humans (Fig. 1): (i) KV7.4 (KCNQ4) maintains outer hair cell (OHC) receptor potential [25–30]; (ii) KV7.1 (KCNQ1) is expressed in marginal cells of the stria vascularis [31–33]; (iii) calcium ion (Ca2+)-activated potassium channels BK (KCNMA1) and SK2 (KCNN2) are involved in repolarization of OHC and termination of Ca2+ action potential (AP) firing in medial olivocochlear (MOC) efferent fibers [34, 35]; and (iv) KV3.1 (KCNC1) in spiral ganglion neurons (SGNs) and ascending auditory circuits [36] are shown to be involved in temporal precision of sound processing [37]
12-month-old C57BL/6 mice displayed notable hearing loss and morphological examination showed a significant OHC loss in the cochlear basal turn accompanied by atrophy of the stria vascularis, with immunohistochemical analysis revealing dramatically decreased KCNJ10 and KCNQ1 expression [144]. While these studies observed a conservation of the endocochlear potential (EP) in these aging C57BL/6 mice, and suggested that the stria vascularis can generate a new balance for potassium influx and efflux at relatively low turnover [144], other studies found a clear requirement of adequate KCNQ1 recycling in marginal stria vascularis membranes for hearing and OHC cell survival [145]
Summary
Age-related hearing loss (ARHL), or presbycusis, is the most prevalent sensory deficit in the elderly [1]. We discuss the following K+ channels with functional expression during or after hearing onset, that is, around postnatal day (P) 12 in rodents, and around embryonic week (EW) 27 in humans (Fig. 1): (i) KV7.4 (KCNQ4) maintains OHC receptor potential [25–30]; (ii) KV7.1 (KCNQ1) is expressed in marginal cells of the stria vascularis [31–33]; (iii) calcium ion (Ca2+)-activated potassium channels BK (KCNMA1) and SK2 (KCNN2) are involved in repolarization of OHC and termination of Ca2+ action potential (AP) firing in medial olivocochlear (MOC) efferent fibers [34, 35]; and (iv) KV3.1 (KCNC1) in SGNs and ascending auditory circuits [36] are shown to be involved in temporal precision of sound processing [37].
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