| First Author | Picher MM | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 9 | Pages | E1717-E1726 |
| PubMed ID | 28183797 | Mgi Jnum | J:255028 |
| Mgi Id | MGI:6113758 | Doi | 10.1073/pnas.1617533114 |
| Citation | Picher MM, et al. (2017) Ca(2+)-binding protein 2 inhibits Ca(2+)-channel inactivation in mouse inner hair cells. Proc Natl Acad Sci U S A 114(9):E1717-E1726 |
| abstractText | Ca(2+)-binding protein 2 (CaBP2) inhibits the inactivation of heterologously expressed voltage-gated Ca(2+) 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 (Cabp2(LacZ/LacZ) ). CaBP2 was expressed by cochlear hair cells, preferentially in inner hair cells (IHCs), and was lacking from the postsynaptic spiral ganglion neurons (SGNs). Cabp2(LacZ/LacZ) mice displayed intact cochlear amplification but impaired auditory brainstem responses. Patch-clamp recordings from Cabp2(LacZ/LacZ) IHCs revealed enhanced Ca(2+)-channel inactivation. The voltage dependence of activation and the number of Ca(2+) channels appeared normal in Cabp2(LacZ/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 Ca(2+)-channel inactivation, and thus sustains the availability of CaV1.3 Ca(2+) channels for synaptic sound encoding. Therefore, we conclude that human deafness DFNB93 is an auditory synaptopathy. |
