α₂δ2 Controls the Function and Trans-Synaptic Coupling of Ca_v1.3 Channels in Mouse Inner Hair Cells and Is Essential for Normal Hearing

Abstract

Inner hair cells possess calcium channels that are essential for transmitting sound information into synaptic transmitter release. Voltage-gated calcium channels can coassemble with auxiliary subunit α₂δ isoforms 1-4. We found that hair cells of the mouse express the auxiliary subunit α₂δ2, which is needed for normal hearing thresholds. Using a mouse model with a mutant, nonfunctional α₂δ2 protein, we showed that the α₂δ2 protein is necessary for normal calcium currents and exocytosis in inner hair cells. Unexpectedly, the α₂δ2 protein is moreover required for the optimal spatial alignment of presynaptic calcium channels and postsynaptic glutamate receptor proteins across the synaptic cleft. This suggests that α₂δ2 plays a novel role in organizing the synapse.