ArticleThe Journal of physiology2008
Expression of the SK2 calcium-activated potassium channel is required for cholinergic function in mouse cochlear hair cells.
Article in The Journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- Drug Discovery Targeting Nicotinic Acetylcholine Receptors for Hearing Loss.International journal of molecular sciences · 2026Review
- Medial Olivocochlear Efferent Modulation of Cochlear Micromechanics Requires P2X4 Receptor in Outer Hair Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Untargeted metabolomics of the cochleae from two laryngeally echolocating bats.Frontiers in molecular biosciences · 2023Article
- Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway.Pflugers Archiv : European journal of physiology · 2021Review
- Sex difference in the efferent inner hair cell synapses of the aging murine cochlea.Hearing research · 2021Article
- SK Current, Expressed During the Development and Regeneration of Chick Hair Cells, Contributes to the Patterning of Spontaneous Action Potentials.Frontiers in cellular neuroscience · 2021Article
- Article
- Loss of α-9 Nicotinic Acetylcholine Receptor Subunit Predominantly Results in Impaired Postural Stability Rather Than Gaze Stability.Frontiers in cellular neuroscience · 2021Article
- Nicotine evoked efferent transmitter release onto immature cochlear inner hair cells.Journal of neurophysiology · 2020Article
- Hair cell α9α10 nicotinic acetylcholine receptor functional expression regulated by ligand binding and deafness gene products.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Efferent synaptic transmission at the vestibular type II hair cell synapse.Journal of neurophysiology · 2020Article
- Effects of Efferent Activity on Hair Bundle Mechanics.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- A review of efferent cholinergic synaptic transmission in the vestibular periphery and its functional implications.Journal of neurophysiology · 2020Review
- Efferent Inhibition of the Cochlea.Cold Spring Harbor perspectives in medicine · 2019Review
- Compartmentalization of antagonistic CaProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Opposing expression gradients of calcitonin-related polypeptide alpha (Calca/Cgrpα) and tyrosine hydroxylase (Th) in type II afferent neurons of the mouse cochlea.The Journal of comparative neurology · 2018Article
- Hair Cell Transduction, Tuning, and Synaptic Transmission in the Mammalian Cochlea.Comprehensive Physiology · 2017Review
- Phosphodiesterase type 2 distribution in the guinea pig urinary bladder.World journal of urology · 2015Article
- Review
- Activation of BK and SK channels by efferent synapses on outer hair cells in high-frequency regions of the rodent cochlea.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Efferent inhibition of cochlear hair cells is mediated by 'nicotinic' cholinergic receptors functionally coupled to calcium-activated, small conductance (SK2) potassium channels. We recorded from cochlear hair cells in SK2 knockout mice to evaluate further the role of this channel in efferent function. Since cholinergic inhibitory synapses can be found on inner or outer hair cells, depending on developmental age, both cell types were studied. To determine if SK channel activity was indeed eliminated, seconds-long voltage-gated calcium influx was used to activate slowly rising and falling calcium-dependent potassium currents. These were identified as SK currents by their time course, calcium dependence and sensitivity to block by apamin in wild-type IHCs. IHCs from knockout mice had no SK current by these same criteria. Thus, the SK2 gene is solely responsible for encoding the SK channels of inner hair cells. Other aspects of hair cell excitability remained relatively unaffected. Unexpectedly, cholinergic synaptic currents were entirely absent from both inner and outer SK2-knockout hair cells. Further, direct application of ACh caused no change in membrane current, implying absent or otherwise dysfunctional ACh receptors. Immunohistology of whole-mounts using the antibody to the synaptic vesicle protein 2 (SV2) revealed a pronounced reduction of efferent innervation to outer hair cells (OHCs) in the knockout cochleas. Quantitative RT-PCR analysis, however, showed no change in the mRNA levels of alpha9 and alpha10 nicotinic ACh receptor (nAChR) genes. Thus, some aspect of translation or subsequent protein processing leads to non-functional or absent ACh receptors. These results indicate that SK2 channels are required both for expression of functional nAChRs, and for establishment and/or maintenance of efferent terminals in the cochlea.
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