Document Detail

Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4.
MedLine Citation:
PMID:  11976689     Owner:  NLM     Status:  MEDLINE    
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 media(). K(+) probably exits outer hair cells by KCNQ4 K(+) channels(), and is then transported by means of a gap junction system connecting supporting Deiters' cells and fibrocytes() 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() 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 syndromes(), 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 alpha-intercalated cells of the distal nephron.
Thomas Boettger; Christian A Hübner; Hannes Maier; Marco B Rust; Franz X Beck; Thomas J Jentsch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  416     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-04-26     Completed Date:  2002-05-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  874-8     Citation Subset:  IM    
Zentrum für Molekulare Neurobiologie, ZMNH, Universität Hamburg, Falkenried 94, 20246 Hamburg, Germany.
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MeSH Terms
Acidosis, Renal Tubular / genetics*,  pathology
Cochlea / metabolism,  pathology
Deafness / genetics*,  pathology
Hair Cells, Auditory / metabolism,  pathology
Hearing Tests
Ion Transport
Kidney / metabolism,  pathology
Mice, Inbred Strains
Potassium / metabolism
Symporters / deficiency*,  genetics*,  metabolism
Reg. No./Substance:
0/SLC12A7 protein, human; 0/Slc12a7 protein, mouse; 0/Symporters; 7440-09-7/Potassium

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