Regulation of the renal Na/K/2Cl cotransporter gene. Physiological modulation in health and abnormal function in disease.

The recently cloned bumetanide-sensitive Na/K/2Cl cotransporters (ENCC2-3) and thiazide-sensitive Na/Cl cotransporter (ENCC1) have important roles in sodium chloride absorption and secretion, cell volume regulation, ammonium accumulation in medullary interstitium, and ammonium excretion. Genetic mutations of bumetanide-sensitive Na/K/2Cl cotransporters and thiazide-sensitive Na/Cl cotransporter cause the hereditary hypokalemic alkalosis of some Bartter's syndrome and Gitelman's syndrome, respectively. The transporters are sensitive to diuretics and several hormones. Dehydration and acidosis influence the gene expression of ENCC3 but not of ENCC1-2. In contrast, sodium loading increases ENCC2 protein expression in the outer medulla.