Role of the calcium-binding protein Sorcin in the auditory system

Intracellular Ca2+ compartmentalization is essential for cochlear outer hair cell (OHC) function, which relies on precise Ca2+ homeostasis. Ca2+ participates in mechanotransduction, synaptic signaling and excitotoxicity associated with noise-induced hearing loss. Transcriptomic studies identified oncomodulin and sorcin among the most highly expressed genes involved in Ca2+ homeostasis in OHCs. While oncomodulin is a well-characterized Ca2+ buffer, the role of sorcin in the cochlea remains unknown. To investigate its contribution to auditory physiology, we used sorcin knockout (KO) mice. Immunohistochemistry confirmed sorcin expression in the cytoplasm of wild-type (WT) OHCs but not in KO mice. Under basal conditions, WT and KO animals showed similar ABR and DPOAE thresholds and amplitudes, indicating that sorcin is not essential for normal auditory function. Preliminary analyses of unexposed cochleae suggest altered presynaptic ribbon organization in KO OHCs. Following noise exposure, both genotypes exhibited comparable hearing loss 1 day post-exposure (dpe). However, WT mice recovered within one week, whereas KO mice showed impaired recovery, maintaining elevated thresholds and reduced amplitudes even 45 dpe. Histological analyses revealed similar afferent synapse loss per inner hair cell in both genotypes, but greater OHC loss in KO mice. Together, these findings suggest that sorcin is not essential for basal hearing but plays a protective role during acoustic stress.