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 function of inner hair cells (IHCs) in the cochlea. The absence of these proteins led to a significant increase in inactivation of IHC CaV1.3 channels, crucial for hearing, and almost completely eliminated sustained exocytosis, necessary for neurotransmission. However, auditory function could be substantially recovered by viral delivery of a CaBP2 coding sequence in the inner ear. The research also found that in CaBP1/2-deficient animals, there were largely inactivated calcium currents with prolonged recovery from inactivation upon mild oscillatory stimulation, impairing proper sound encoding. Overexpression of CaBP2 in IHCs resulted in a partial recovery of the Ca2+ influx and an even better recovery of exocytosis. The study involved mice models and was approved by the University of Göttingen Board for animal welfare and the animal welfare office of the state of Lower Saxony.