CaBP1 and 2 enable sustained Ca_V1.3 calcium currents and synaptic transmission in inner hair cells.

ABSTRACT: To encode continuous sound stimuli, the inner hair cell (IHC) ribbon synapses utilize calcium-binding proteins (CaBPs), which reduce the inactivation of their Ca_V1.3 calcium channels. Mutations in the CABP2 gene underlie non-syndromic autosomal recessive hearing loss DFNB93. Besides CaBP2, the structurally related CaBP1 is highly abundant in the IHCs. Here, we investigated how the two CaBPs cooperatively regulate IHC synaptic function. In Cabp1/2 double-knockout mice, we find strongly enhanced Ca_V1.3 inactivation, slowed recovery from inactivation and impaired sustained exocytosis. Already mild IHC activation further reduces the availability of channels to trigger synaptic transmission and may effectively silence synapses. Spontaneous and sound-evoked re

SUBMITTER: Oestreicher D 

PROVIDER: S-EPMC11668525 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature