Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation

Modulation of voltage-gated calcium channels was studied in inner hair cells (IHCs) in an ex vivo preparation of the apical turn of the rat organ of Corti. Whole cell voltage clamp in the presence of potassium channel blockers showed inward calcium currents with millisecond activation and deactivation kinetics. When temperature was raised from 22 to 37°C, the calcium currents of immature IHCs [<12 days postnatal (P12)] increased threefold in amplitude, and developed more pronounced inactivation. This was determined to be calcium-dependent inactivation (CDI) on the basis of its reliance on external calcium (substitution with barium), sensitivity to internal calcium-buffering, and voltage dependence (reflecting the calcium driving force). After the onset of hearing at P12, IHC calcium current amplitude and the extent of inactivation were greatly reduced. Although smaller than in prehearing IHCs, CDI remained significant in the mature IHC near the resting membrane potential. CDI in mature IHCs was enhanced by application of the endoplasmic calcium pump blocker, benzo-hydroquinone. Conversely, CDI in immature IHCs was reduced by calmodulin inhibitors. Thus voltage-gated calcium channels in mammalian IHCs are subject to a calmodulin-mediated process of CDI. The extent of CDI depends on the balance of calcium buffering mechanisms and may be regulated by calmodulin-specific processes. CDI provides a means for the rate of spontaneous transmitter release to be adjusted to variations in hair cell resting potential and steady state calcium influx.

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Sodium and calcium currents shape action potentials in immature mouse inner hair cells

The Journal of Physiology ◽

10.1113/jphysiol.2003.043612 ◽

2003 ◽

Vol 552 (3) ◽

pp. 743-761 ◽

Cited By ~ 118

Author(s):

Walter Marcotti ◽

Stuart L. Johnson ◽

Alfons Rüsch ◽

Corné J. Kros

Keyword(s):

Hair Cells ◽

Action Potentials ◽

Calcium Currents ◽

Inner Hair Cells ◽

Immature Mouse

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Exposure to Sodium Salicylate Disrupts VGLUT3 Expression in Cochlear Inner Hair Cells and Contributes to Tinnitus

Physiological Research ◽

10.33549/physiolres.934180 ◽

2020 ◽

pp. 181-190 ◽

Cited By ~ 1

Author(s):

W. ZHANG ◽

Z. PENG ◽

S. YU ◽

Q.-L. SONG ◽

T.-F. QU ◽

...

Keyword(s):

Hair Cells ◽

Cochlear Nucleus ◽

Sodium Salicylate ◽

Acoustic Startle ◽

Auditory Brainstem ◽

Acoustic Startle Reflex ◽

Saline Control ◽

Inner Hair Cells ◽

Increased Risk ◽

Brainstem Response

To examine whether exposure to sodium salicylate disrupts expression of vesicular glutamate transporter 3 (VGLUT3) and whether the alteration in expression corresponds to increased risk for tinnitus. Rats were treated with saline (control) or sodium salicylate (treated) Rats were examined for tinnitus by monitoring gap-pre-pulse inhibition of the acoustic startle reflex (GPIAS). Auditory brainstem response (ABR) was applied to evaluate hearing function after treatment. Rats were sacrificed after injection to obtain the cochlea, cochlear nucleus (CN), and inferior colliculus (IC) for examination of VGLUT3 expression. No significant differences in hearing thresholds between groups were identified (p>0.05). Tinnitus in sodium salicylate-treated rats was confirmed by GPIAS. VGLUT3 encoded by solute carrier family 17 members 8 (SLC17a8) expression was significantly increased in inner hair cells (IHCs) of the cochlea in treated animals, compared with controls (p<0.01). No significant differences in VGLUT3 expression between groups were found for the cochlear nucleus (CN) or IC (p>0.05). Exposure to sodium salicylate may disrupt SLC17a8 expression in IHCs, leading to alterations that correspond to tinnitus in rats. However, the CN and IC are unaffected by exposure to sodium salicylate, suggesting that enhancement of VGLUT3 expression in IHCs may contribute to the pathogenesis of tinnitus.

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Faculty Opinions recommendation of Inner hair cells are not required for survival of spiral ganglion neurons in the adult cochlea.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13483964.14861062 ◽

2012 ◽

Author(s):

Andy Groves

Keyword(s):

Hair Cells ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Inner Hair Cells ◽

Ganglion Neurons

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Faculty Opinions recommendation of LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736503545.793580199 ◽

2020 ◽

Author(s):

Tobias Moser

Keyword(s):

Hair Cells ◽

Bk Channel ◽

Inner Hair Cells ◽

Channel Function

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Inner hair cell stereocilia are embedded in the tectorial membrane

Nature Communications ◽

10.1038/s41467-021-22870-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Pierre Hakizimana ◽

Anders Fridberger

Keyword(s):

Electron Microscopy ◽

Hair Cell ◽

Mechanical Stimulation ◽

Hair Cells ◽

Viscous Drag ◽

Tectorial Membrane ◽

Inner Hair Cell ◽

Inner Hair Cells ◽

Inward Currents

AbstractMammalian hearing depends on sound-evoked displacements of the stereocilia of inner hair cells (IHCs), which cause the endogenous mechanoelectrical transducer channels to conduct inward currents of cations including Ca2+. Due to their presumed lack of contacts with the overlaying tectorial membrane (TM), the putative stimulation mechanism for these stereocilia is by means of the viscous drag of the surrounding endolymph. However, despite numerous efforts to characterize the TM by electron microscopy and other techniques, the exact IHC stereocilia-TM relationship remains elusive. Here we show that Ca2+-rich filamentous structures, that we call Ca2+ ducts, connect the TM to the IHC stereocilia to enable mechanical stimulation by the TM while also ensuring the stereocilia access to TM Ca2+. Our results call for a reassessment of the stimulation mechanism for the IHC stereocilia and the TM role in hearing.

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