Chloride channels in renal disease.
Recent studies of hereditary renal tubular disorders have facilitated the identification and roles of chloride channels and cotransporters in the regulation of the most abundant anion, Cl-, in the ECF. Thus, mutations that result in a loss of function of the voltage-gated chloride channel, CLC-5, are associated with Dent's disease, which is characterized by low-molecular weight proteinuria, hypercalciuria, nephrolithiasis, and renal failure. Mutations of another voltage-gated chloride channel, CLC-Kb, are associated with a form of Bartter's syndrome, whereas other forms of Bartter's syndrome are caused by mutations in the bumetanide-sensitive sodium-potassium-chloride cotransporter (NKCC2) and the potassium channel, ROMK. Finally, mutations of the thiazide-sensitive sodium-chloride cotransporter (NCCT) are associated with Gitelman's syndrome. These studies have helped to elucidate some of the renal tubular mechanisms regulating mineral homeostasis and the role of chloride channels.
Thakker
R V
RV
MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, England.
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001477:Bartter Syndrome / Q000235:genetics; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics; D007674:Kidney Diseases / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation / Q000502:physiology
D018118:Chloride Channels