Molecular Correlates Of Hearing Loss: Oncomodulin And Prestin

Abstract

The exquisite hearing sensitivity of mammalian hearing is due to cochlear outer hair cells (OHCs) that amplify sound signals through changes in cell membrane potential and cell length. The OHC motor protein, prestin, is responsible for this phenomenon. Oncomodulin (OCM) is the dominant calcium-binding protein in OHCs and therefore plays a major role in calcium homeostasis. Adult Ocm knockout (KO) mice are deaf and prestin expression is abnormally distributed. Since prestin and OCM are localized in the periphery of OHCs, we hypothesized that they may interact. We performed high- resolution confocal imaging in adult wildtype (WT) mice at various ages. Measures of labeling intensity found OCM and prestin labeling in OHCs colocalized. Since prestin is expressed in Ocm-KO mice, we hypothesized that increasing prestin expression might delay hearing loss in Ocm-KO mice. Previous studies show that long-term administration of nonsteroidal anti-inflammatory drugs increases prestin protein expression, OHC electromotility and improved hearing. We performed salicylate injections in Ocm-KO mice to potentially delay hearing loss. Although we found that salicylate had an effect in WT mice, there was no or little effect in Ocm-KO mice. Taken together, our results suggest that the loss of OCM may have deleterious effects on prestin function in OHCs.