Research Report 2010 - MDC

Figure 2. Cellular model for ionic transport across the stria vascularis. In this multilayered epithelium, potassium is secreted across the apicalmembrane of marginal cells through KCNQ1/KCNE1 K + -channels. Potassium is taken up basolaterally through the combined transport activity ofthe Na,K-ATPase and the NaK2Cl cotransporter NKCC1. The latter transporter needs Cl - channels for recyling. Our work has shown that this task iscarried out by ClC-Ka/barttin and ClC-Kb/barttin Cl - channels. If the β-subunit is missing as in patients with Bartter syndrome type IV or in ourKO mouse model, potassium secretion is impaired and the K + -concentration in the extracellular space between marginal and intermediate cellsincreases. This leads to a dramatic drop of the endocochlear potential, which is largely generated by a K + -diffusion potential through Kir4.1K + -channels in the apical membrane in intermediate cells. This drop in potential leads to deafness.Figure 3. Selective degeneration of outer hair cells in barttin KO mice. The drop in endocochlear potential owed to a loss of barttin leadsto a functional impairment of outer hair cells and later also to their degeneration, as shown by immunocytochemistry (upper row; innerhair cells stained in red, outer hair cells in green) and hematoxin-eosin staining (below, outer hair cells indicated by arrows).156 Function and Dysfunction of the Nervous System