title: New perspective of ClC-Kb/2 Cl- channel physiology in the distal renal tubule.
abstract: Since its identification as the underlying molecular cause of Bartter's syndrome type 3, ClC-Kb (ClC-K2 in rodents, henceforth it will be referred as ClC-Kb/2) is proposed to play an important role in systemic electrolyte balance and blood pressure regulation by controlling basolateral Cl(-) exit in the distal renal tubular segments from the cortical thick ascending limb to the outer medullary collecting duct. Considerable experimental and clinical effort has been devoted to the identification and characterization of disease-causing mutations as well as control of the channel by its cofactor, barttin. However, we have only begun to unravel the role of ClC-Kb/2 in different tubular segments and to reveal the regulators of its expression and function, e.g., insulin and IGF-1. In this review we discuss recent experimental evidence in this regard and highlight unexplored questions critical to understanding ClC-Kb/2 physiology in the kidney.
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, Texas; and Oleg.L.Zaika@uth.tmc.edu.
authors.forename: Oleg
authors.initials: O
authors.lastname: Zaika
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, Texas; and.
authors.forename: Viktor
authors.initials: V
authors.lastname: Tomilin
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, Texas; and.
authors.forename: Mykola
authors.initials: M
authors.lastname: Mamenko
authors.affiliation: Division of Nephrology, Department of Medicine, Stanford University, Stanford, California.
authors.forename: Vivek
authors.initials: V
authors.lastname: Bhalla
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, Texas; and.
authors.forename: Oleh
authors.initials: O
authors.lastname: Pochynyuk
mesh_terms: D000818:Animals; D001477:Bartter Syndrome / Q000235:genetics; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000378:metabolism*
chemical_list: D018118:Chloride Channels; D007328:Insulin; D007334:Insulin-Like Growth Factor I
keywords: chloride ion reabsorption; collecting duct; distal convoluted tuble; pH balance; thick ascending limb