Na‐K‐ATPase activity involved in noise induced blood‐labyrinth‐barrier leakage

Abstract

Na+/K+‐ATPase plays an important role in mediating barrier integrity in the polarized epithelial cells. In the cochlea, we found that Na+/K+‐ATPase subunit alpha 1 was the most abundant protein of the vascular tissue in the blood‐labyrinth‐barrier (BLB) and was expressed predominantly at the luminal side of the endothelium. Na‐K‐ATPase is known to be required for controlling the tight junctions in epithelial cells. In this study, we investigated the involvement of Na+/K+‐ATPase in noise induced BLB leakage. In mice, the expression and activity of Na+/K+‐ATPase were found to be correlated with the changes of expression of tight junction proteins as well as the change in BLB permeability. Increased expression of Na+/K+‐ATPase, at both transcriptional and protein levels, occurred after noise exposure at 120 dB SPL for 3h per day for two days. However, Na+/K+‐ATPase enzymatic activity was significantly decreased. There was a significant decrease in endothelial tight junction membrane contact points. In vitro inhibition of Na+, K+‐ATPase by ouabain corroborated the in vivo studies and showed swelling of capillary endothelial cells and increased ratio between occludin phosphorylation and dephosphorylation. The results support a functional link between Na+, K+‐ATPase and occludin in the BLB as one of the mechanisms for noise induced in the BLB.Support: NIDCD DC 00888, NIDCD DC 00105, NIDCD DC 005983 (p30)