CaBP1 and 2 Enable Sustained CaV1.3 Calcium Currents and Synaptic Transmission in Inner Hair Cells

The study investigates the role of calcium-binding proteins CaBP1 and CaBP2 in the inactivation of calcium currents in cochlear inner hair cells. Using a mouse model lacking both CaBP1 and CaBP2, the authors demonstrate that both proteins together prevent inactivation, with CaBP2 being more effective. This lack of inactivation is crucial for the continuous sound encoding by inner hair cells. The study also shows that reintroducing CaBP2 through viral gene transfer into the inner ear of double-knockout mice largely restored hearing function, normal calcium current properties, and exocytosis. However, the study does not clarify how CaBP1 and CaBP2 work together or the effect of reintroducing only CaBP1. The findings contribute to understanding the regulation of Cav1.3 currents, crucial for sensory transduction, and better explain the phenotype of the human autosomal recessive DFNB93, which is based on the malfunction of CaBP2.