Channelpedia

PubMed 15752747


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC4 , ClvC5



Title: Impaired acidification in early endosomes of ClC-5 deficient proximal tubule.

Authors: Mariko Hara-Chikuma, Yinghong Wang, Sandra E Guggino, William B Guggino, A S Verkman

Journal, date & volume: Biochem. Biophys. Res. Commun., 2005 Apr 15 , 329, 941-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15752747


Abstract
ClC-5 chloride channel deficiency causes proteinuria, hypercalciuria, and nephrolithiasis (Dent's disease). Impaired endosomal acidification in proximal tubule caused by reduced chloride conductance is a proposed mechanism; however, functional analysis of ClC-5 in oocytes predicts low ClC-5 chloride conductance in endosomes because of their acid interior pH and positive potential. Here, endosomal pH and chloride concentration were measured in proximal tubule cell cultures from wildtype vs. ClC-5 deficient mice using fluorescent sensors coupled to transferrin (early/recycling endosomes) or alpha(2)-macroglobulin (late endosomes). Initial pH in transferrin-labeled endosomes was approximately 7.2, decreasing at 15 min to 6.0 vs. 6.5 in wildtype vs. ClC-5 deficient cells, respectively; corresponding endosomal chloride concentration increased from approximately 16 mM to 47 vs. 36 mM. In contrast, acidification and chloride accumulation were not impaired in late endosomes or Golgi. Our results provide direct evidence for ClC-5 involvement in acidification of early endosomes in proximal tubule by a chloride shunt mechanism.