1. Zentrum für Molekulare Neurobiologie, ZMNH, Universität Hamburg, Falkenried 94, 20246 Hamburg, Germany
2. HNO Klinik, Universitätsklinikum Eppendorf, Universität Hamburg, Martinistrasse 52, 20246 Hamburg, Germany
3. Physiologisches Institut, Ludwig-Maximilians-Universität München, Pettenkoferstrasse 12, 80336 München, Germany
4. These authors contributed equally to this work

Correspondence to: Thomas J. Jentsch¹ Correspondence and requests for materials should be addressed to T.J.J. (e-mail: Email: jentsch@zmnh.uni-hamburg.de).

Abstract

Hearing depends on a high K⁺ concentration bathing the apical membranes of sensory hair cells. K⁺ that has entered hair cells through apical mechanosensitive channels is transported to the stria vascularis for re-secretion into the scala media¹. K⁺ probably exits outer hair cells by KCNQ4 K⁺ channels^{2, 3}, and is then transported—by means of a gap junction system connecting supporting Deiters' cells and fibrocytes⁴—back to the stria vascularis. We show here that mice lacking the K⁺/Cl^- (K-Cl) co-transporter Kcc4 (coded for by Slc12a7) are deaf because their hair cells degenerate rapidly after the beginning of hearing. In the mature organ of Corti, Kcc4 is restricted to supporting cells of outer and inner hair cells. Our data suggest that Kcc4 is important for K⁺ recycling^{1, 5} by siphoning K⁺ ions after their exit from outer hair cells into supporting Deiters' cells, where K⁺ enters the gap junction pathway. Similar to some human genetic syndromes⁶, deafness in Kcc4-deficient mice is associated with renal tubular acidosis. It probably results from an impairment of Cl^- recycling across the basolateral membrane of acid-secreting -intercalated cells of the distal nephron.