The Ca2+ Channel Subunit beta 2 Regulates Ca2+ Channel Abundance and Function in Inner Hair Cells and Is Required for Hearing
2009 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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The Ca2+ Channel Subunit beta 2 Regulates Ca2+ Channel Abundance and Function in Inner Hair Cells and Is Required for Hearing
Neef, J. ; Gehrt, A. ; Bulankina, A. V.; Meyer, A. C.; Riedel, D. ; Gregg, R. G. & Strenzke, N. et al. (2009)
The Journal of neuroscience, 29(34) pp. 10730-10740. DOI: https://doi.org/10.1523/JNEUROSCI.1577-09.2009
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- Authors
- Neef, Jakob ; Gehrt, Anna ; Bulankina, Anna V.; Meyer, Alexander C.; Riedel, Dietmar ; Gregg, Ronald G.; Strenzke, Nicola ; Moser, Tobias
- Abstract
- Hearing relies on Ca2+ influx-triggered exocytosis in cochlear inner hair cells (IHCs). Here we studied the role of the Ca2+ channel subunit Ca-V beta(2) in hearing. Of the Ca-V beta(1-4) mRNAs, IHCs predominantly contained Ca-V beta(2). Hearing was severely impaired in mice lacking Ca-V beta(2) in extracardiac tissues (Ca-V beta(-/-)(2)). This involved deficits in cochlear amplification and sound encoding. Otoacoustic emissions were reduced or absent in Ca-V beta(-/-)(2) mice, which showed strongly elevated auditory thresholds in single neuron recordings and auditory brainstem response measurements. Ca-V beta(-/-)(2) IHCs showed greatly reduced exocytosis (by 68%). This was mostly attributable to a decreased number of membrane-standing Ca(V)1.3 channels. Confocal Ca2+ imaging revealed presynaptic Ca2+ microdomains albeit with much lower amplitudes, indicating synaptic clustering of fewer Ca(V)1.3 channels. The coupling of the remaining Ca2+ influx to IHC exocytosis appeared unaffected. Extracellular recordings of sound-evoked spiking in the cochlear nucleus and auditory nerve revealed reduced spike rates in the Ca-V beta(-/-)(2) mice. Still, sizable onset and adapted spike rates were found during suprathreshold stimulation in Ca-V beta 2(-/-) mice. This indicated that residual synaptic sound encoding occurred, although the number of presynaptic Ca(V)1.3 channels and exocytosis were reduced to one-third. The normal developmental upregulation, clustering, and gating of large-conductance Ca2+ activated potassium channels in IHCs were impaired in the absence of Ca-V beta(2). Moreover, we found the developmental efferent innervation to persist in Ca-V beta(2)-deficient IHCs. In summary, Ca-V beta(2) has an essential role in regulating the abundance and properties of Ca(V)1.3 channels in IHCs and, thereby, is critical for IHC development and synaptic encoding of sound.
- Issue Date
- 2009
- Publisher
- Soc Neuroscience
- Journal
- The Journal of neuroscience
- ISSN
- 0270-6474