In vivo role of CLC chloride channels in the kidney.
Chloride channels in the kidney are involved in important physiological functions such as cell volume regulation, acidification of intracellular vesicles, and transepithelial chloride transport. Among eight mammalian CLC chloride channels expressed in the kidney, three (CLC-K1, CLC-K2, and CLC-5) were identified to be related to kidney diseases in humans or mice. CLC-K1 mediates a transepithelial chloride transport in the thin ascending limb of Henle's loop and is essential for urinary concentrating mechanisms. CLC-K2 is a basolateral chloride channel in distal nephron segments and is necessary for chloride reabsorption. CLC-5 is a chloride channel in intracellular vesicles of proximal tubules and is involved in endocytosis. This review will cover the recent advances in research on the CLC chloride channels of the kidney with a special focus on the issues most necessary to understand their physiological roles in vivo, i.e., their intrarenal and cellular localization and their phenotypes of humans and mice that have their loss-of-function mutations.
Uchida
S
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Second Department of Internal Medicine, Tokyo Medical and Dental University, School of Medicine, Tokyo 113-8519, Japan. suchida.med2@med.tmd.ac.jp
D000818:Animals; D027321:Anion Transport Proteins; D001477:Bartter Syndrome / Q000235:genetics; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D029867:Xenopus Proteins; D014982:Xenopus laevis
D027321:Anion Transport Proteins; C097503:CLC-5 chloride channel; C489932:CLCNKA protein, human; C412733:CLCNKB protein, human; D018118:Chloride Channels; C489933:Clcnka protein, mouse; C082118:Clcnka protein, rat; C486573:Clcnkb protein, mouse; C486572:Clcnkb protein, rat; D008565:Membrane Proteins; D029867:Xenopus Proteins; C489934:clcnka protein, Xenopus