Sensorineural Hearing Loss and Dyslipidemia

Campbell, Kathleen C.M.; Rybak, Leonard P.; Khardori, Romesh

doi:10.1044/1059-0889.0503.11

Cited by 12 publications

(10 citation statements)

References 34 publications

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“…The modulation of VGCC and BK currents by cholesterol, and the associated changes in hair cell excitability,may have implications for sensorineural hearing loss.While the mechanism is unknown and is likely to be multi-faceted, there is a correlation between hearing loss and dyslipidemia [39] . Calcium influx through VGCCs clustered in nanodomains causes exocytosis and neurotransmitter release at the inner hair cell base, and VGCC dysfunction has been linked to deafness in humans [35] , [40] , [41] .…”

Section: Discussionmentioning

confidence: 99%

Cholesterol Influences Voltage-Gated Calcium Channels and BK-Type Potassium Channels in Auditory Hair Cells

et al. 2011

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The influence of membrane cholesterol content on a variety of ion channel conductances in numerous cell models has been shown, but studies exploring its role in auditory hair cell physiology are scarce. Recent evidence shows that cholesterol depletion affects outer hair cell electromotility and the voltage-gated potassium currents underlying tall hair cell development, but the effects of cholesterol on the major ionic currents governing auditory hair cell excitabilityare unknown. We investigated the effects of a cholesterol-depleting agent (methyl beta cyclodextrin, MβCD) on ion channels necessary for the early stages of sound processing. Large-conductance BK-type potassium channels underlie temporal processing and open in a voltage- and calcium-dependent manner. Voltage-gated calcium channels (VGCCs) are responsible for calcium-dependent exocytosis and synaptic transmission to the auditory nerve. Our results demonstrate that cholesterol depletion reduced peak steady-state calcium-sensitive (BK-type) potassiumcurrent by 50% in chick cochlear hair cells. In contrast, MβCD treatment increased peak inward calcium current (∼30%), ruling out loss of calcium channel expression or function as a cause of reduced calcium-sensitive outward current. Changes in maximal conductance indicated a direct impact of cholesterol on channel number or unitary conductance. Immunoblotting following sucrose-gradient ultracentrifugation revealed BK expression in cholesterol-enriched microdomains. Both direct impacts of cholesterol on channel biophysics, as well as channel localization in the membrane, may contribute to the influence of cholesterol on hair cell physiology. Our results reveal a new role for cholesterol in the regulation of auditory calcium and calcium-activated potassium channels and add to the growing evidence that cholesterol is a key determinant in auditory physiology.

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Section: Discussionmentioning

confidence: 99%

Cholesterol Influences Voltage-Gated Calcium Channels and BK-Type Potassium Channels in Auditory Hair Cells

et al. 2011

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“…An association between HL and elevated cholesterol has previously been reported although not just in older individuals as we found. 21 Studies of the relationship between diabetes, HL, and noise have had conflicting results. [22][23][24] The prevalence of workrelated HL was significantly higher in our study among those who had been diagnosed with diabetes compared with those who had not.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Hearing Loss and Work-Related Noise-Induced Hearing Loss in Michigan

Stanbury

Rafferty

Rosenman

2008

Journal of Occupational &Amp; Environmental Medicine

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“…In afferently-innervated hair cells, CLR modulation of BK currents could reshape electrical potentials, alter tuning and temporal coding and, by changing the membrane time constant, the capability of the cell to accurately respond to repetitive stimuli (Purcell et al, 2011). Interestingly, these authors point to a correlation between hearing loss and dyslipidemia (Campbell et al, 1996). …”

Section: Pathophysiological Implications and Concluding Remarksmentioning

confidence: 99%

Large conductance, calcium- and voltage-gated potassium (BK) channels: Regulation by cholesterol

Dopico

Bukiya

Singh

2012

Pharmacology & Therapeutics

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Sensorineural Hearing Loss and Dyslipidemia

Cited by 12 publications

References 34 publications

Cholesterol Influences Voltage-Gated Calcium Channels and BK-Type Potassium Channels in Auditory Hair Cells

Cholesterol Influences Voltage-Gated Calcium Channels and BK-Type Potassium Channels in Auditory Hair Cells

Prevalence of Hearing Loss and Work-Related Noise-Induced Hearing Loss in Michigan

Large conductance, calcium- and voltage-gated potassium (BK) channels: Regulation by cholesterol

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