The Na-K-Cl Cotransporters

摘要: The Na-K-Cl cotransporters are a class of membrane proteins that transport Na, K, and Cl ions into out wide variety epithelial nonepithelial cells. process mediated by is characterized electroneutrality (almost always with stoichiometry 1Na:1K:2Cl) inhibition the "loop" diuretics bumetanide, benzmetanide, furosemide. Presently, two distinct cotransporter isoforms have been identified cDNA cloning expression; genes encoding these located on different chromosomes their gene products share approximately 60% amino acid sequence identity. NKCC1 (CCC1, BSC2) isoform present in tissues; most epithelia containing secretory localized to basolateral membrane. By contrast, NKCC2 (CCC2, BSC1) found only kidney, apical cells thick ascending limb Henle's loop macula densa. Mutations result Bartter's syndrome, an inherited disease hypokalemic metabolic alkalosis, hypercalciuria, salt wasting, volume depletion. also part superfamily cation-chloride cotransporters, which includes electroneutral K-Cl Na-Cl cotransporters. activity affected large hormonal stimuli as well changes cell volume; many tissues this regulation (particularly NKCCI isoform) occurs through direct phosphorylation/dephosphorylation cotransport protein itself though specific kinases involved remain unknown. An important regulator other intracellular [Cl] ([Cl]i), reduction [Cl]i being apparent means increased thus coordinated stimulated channels actively secreting epithelia.