Ca2+-binding protein 2 inhibits Ca2+-channel inactivation in mouse inner hair cells
2017-02-28 | journal article
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Ca2+-binding protein 2 inhibits Ca2+-channel inactivation in mouse inner hair cells
Picher, M. M. ; Gehrt, A. ; Meese, S. ; Ivanovic, A. ; Predoehl, F. ; Jung, S. & Schrauwen, I. et al. (2017)
Proceedings of the National Academy of Sciences of the United States of America, 114(9) pp. E1717-E1726. DOI: https://doi.org/10.1073/pnas.1617533114
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Details
- Authors
- Picher, Maria Magdalena ; Gehrt, Anna ; Meese, Sandra ; Ivanovic, Aleksandra ; Predoehl, Friederike ; Jung, SangYong ; Schrauwen, Isabelle; Dragonetti, Alberto Giulio; Colombo, Roberto; Van Camp, Guy; Strenzke, Nicola ; Moser, Tobias
- Abstract
- Ca2+-binding protein 2 (CaBP2) inhibits the inactivation of heterologously expressed voltage-gated Ca2+ channels of type 1.3 (CaV1.3) and is defective in human autosomal-recessive deafness 93 (DFNB93). Here, we report a newly identified mutation in CABP2 that causes a moderate hearing impairment likely via nonsense-mediated decay of CABP2-mRNA. To study the mechanism of hearing impairment resulting from CABP2 loss of function, we disrupted Cabp2 in mice (Cabp2LacZ/LacZ ). CaBP2 was expressed by cochlear hair cells, preferentially in inner hair cells (IHCs), and was lacking from the postsynaptic spiral ganglion neurons (SGNs). Cabp2LacZ/LacZ mice displayed intact cochlear amplification but impaired auditory brainstem responses. Patch-clamp recordings from Cabp2LacZ/LacZ IHCs revealed enhanced Ca2+-channel inactivation. The voltage dependence of activation and the number of Ca2+ channels appeared normal in Cabp2LacZ/LacZ mice, as were ribbon synapse counts. Recordings from single SGNs showed reduced spontaneous and sound-evoked firing rates. We propose that CaBP2 inhibits CaV1.3 Ca2+-channel inactivation, and thus sustains the availability of CaV1.3 Ca2+ channels for synaptic sound encoding. Therefore, we conclude that human deafness DFNB93 is an auditory synaptopathy.
- Issue Date
- 28-February-2017
- Journal
- Proceedings of the National Academy of Sciences of the United States of America
- eISSN
- 1091-6490
- Language
- English