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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

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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 1

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Diverse roles of Cl– channels in transepithelial transport. In colonic e...
Diverse roles of Cl– channels in transepithelial transport. In colonic epithelia, cells at the luminal surface (A) express a Cl–/HCO3– exchanger (which may be electrogenic) and the Na+/H+ exchanger NHE3 in their apical membrane, allowing for net NaCl reabsorption. Chloride probably crosses the basolateral membrane through ClC-2. Cells at the crypt base (B) secrete chloride, which is taken up by basolateral NKCC1, through apical CFTR channels. KCNQ1/KCNE3 heteromeric K+ channels are needed for K+ recycling. (C) Model for K+ secretion in the stria vascularis of the cochlea. K+ is taken up by the basolateral isoform of the NKCC cotransporter, NKCC1, and the Na,K-ATPase. Chloride is recycled by basolateral ClC-Ka and ClC-Kb/barttin channels. (D) Model for NaCl reabsorption in the thick ascending limb of Henle (TAL). NaCl is taken up by the apical NKCC2 transporter that needs the apical ROMK channel for K+ recycling. Cl– leaves the cell through basolateral ClC-Kb/barttin channels. (E) Model for intercalated cells of the collecting duct. α-Intercalated cells (α-IC) secrete protons using a proton ATPase, while basolateral transport of acid equivalents is via the anion exchanger AE1. It is proposed that both KCC4 cotransporters (65) and ClC-K/barttin channels recycle Cl–. It is unknown whether ClC-K/barttin is involved in Cl– reabsorption in β-intercalated cells as shown below.

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