Salicylates Decrease AQP6 Expression in the Mouse Organ of Corti

Salicylates are well-known for their reversible ototoxic effect. Among their actions in the ear there is a direct inhibition of the OHC molecular motor prestin (Oliver et al. 2001). However, the ear contains other targets for these drugs, notably cyclo-oxygenases (COX; Stjernschantz et al. 2004), which are key enzymes in the synthetic pathway of prostaglandins. Among the targets of prostaglandins are aquaporins, which form water channels in lipid membranes, thus regulating volume and concentration of cellular and subcellular compartments. Several aquaporins are expressed in the inner ear (Ishiyama et al. 2006), but their role is still largely unclear. In the present work we have studied the expression of AQP6 in the mouse cochlea, by immunolabeling of paraffin-embedded cochlear sections, in control conditions and after salicylate treatment. AQP6 was observed in the spiral ganglion, and within the organ of Corti at the level of Deiters' and phalangeal cells. After treatment with salicylates, AQP6 labeling of the organ of Corti was dramatically reduced. This appears interesting, because Deiters' and phalangeal cells represent the "entry points" to epitelial cell gap-junction-coupled systems involved in K+ recycling (Kikuchi et al. 2000). The role played by AQP6 could involve both water and ionic homeostasis, since this aquaporin isoform displays both water and Cl- permeability (Nagase et al. 2007).