Expression of CLC-K chloride channels in the rat cochlea.
Current models of the lateral K+ recycling pathway in the mammalian cochlea include two multicellular transport networks separated from one another by three interstitial gaps. The first gap is between outer hair cells and Deiters cells, the second is between outer sulcus cells and type II spiral ligament fibrocytes and the third is between intermediate and marginal cells in the stria vascularis. K+ taken up by cells bordering these interstitial spaces is accompanied by Cl-. Maintaining appropriate electrolyte balance and membrane potentials in these cells requires a mechanism for exit of the resorbed Cl-. One possible candidate for regulating this Cl- efflux is ClC-K, a chloride channel previously thought to be kidney specific. Here, we demonstrate the expression of both known isoforms of ClC-K in the organ of Corti, spiral ligament and stria vascularis of the rat cochlea by immunohistochemical, Western blot and RT-PCR analysis. These results indicate a role for ClC-K in mediating Cl- recycling in the cochlea. The widespread expression of both ClC-K isoforms in the cochlea may help to explain the symptoms of Bartter's syndrome Type III, a mutation in the hClC-Kb gene (human homologue of ClC-K2), which results in renal salt wasting without deafness. These data support the hypothesis that both isoforms of ClC-K are co-expressed in some cell membranes and account for the preservation of hearing in the presence of a mutation in only one channel isoform.
Qu
Chunyan
C
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 165 Ashley Avenue, Suite 309, P.O. Box 250908, Charleston, SC 29425, USA. quc@musc.edu
Liang
Fenghe
F
Hu
Wei
W
Shen
Zhijun
Z
Spicer
Samuel S
SS
Schulte
Bradley A
BA
D000818:Animals; D000831:Animals, Newborn; D027321:Anion Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D018118:Chloride Channels / Q000096:biosynthesis* / Q000235:genetics; D003051:Cochlea / Q000378:metabolism*; D003053:Cochlear Duct / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009925:Organ of Corti / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013316:Stria Vascularis / Q000378:metabolism
D027321:Anion Transport Proteins; D018118:Chloride Channels; C082118:Clcnka protein, rat; C486572:Clcnkb protein, rat; D008565:Membrane Proteins; D012333:RNA, Messenger