Chloride channel diseases resulting from impaired transepithelial transport or vesicular function
Thomas J. Jentsch, … , Tanja Maritzen, Anselm A. Zdebik
Thomas J. Jentsch, … , Tanja Maritzen, Anselm A. Zdebik
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2039-2046. https://doi.org/10.1172/JCI25470.
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Chloride channel diseases resulting from impaired transepithelial transport or vesicular function

Abstract

The transport of anions across cellular membranes is crucial for various functions, including the control of electrical excitability of muscle and nerve, transport of salt and water across epithelia, and the regulation of cell volume or the acidification and ionic homeostasis of intracellular organelles. Given this broad range of functions, it is perhaps not surprising that mutations in Cl– channels lead to a large spectrum of diseases. These diverse pathologies include the muscle disorder myotonia, cystic fibrosis, renal salt loss in Bartter syndrome, kidney stones, deafness, and the bone disease osteopetrosis. This review will focus on diseases related to transepithelial transport and on disorders involving vesicular Cl– channels.

Authors

Thomas J. Jentsch, Tanja Maritzen, Anselm A. Zdebik

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Figure 2

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General concept of vesicular acidification exemplified by ClC-7. (A) Ves...
General concept of vesicular acidification exemplified by ClC-7. (A) Vesicles of the endosomal and lysosomal pathway are acidified by H+-ATPases. Their current is neutralized by Cl– channels. In their absence, efficient proton pumping is prevented. (B) Model for the resorption lacuna acidification in osteoclasts. The H+-ATPase and ClC-7 are trafficked to the “ruffled border” membrane of osteoclasts. The acidification of the resorption lacuna is required for dissolving the mineral phase of bone, as well as for the enzymatic degradation of the organic bone matrix by lysosomal enzymes. It depends on the presence of both ClC-7 and the H+-ATPase in the ruffled border.