Mammalian distal tubule: Physiology, pathophysiology, and molecular anatomy

The distal tubule of the mammalian kidney, defined as the region between th e macula densa and the collecting duct, is morphologically and functionally heterogeneous. This heterogeneity has stymied attempts to define functiona l properties of individual cell types and has led to controversy concerning mechanisms and regulation of ion transport. Recently, molecular techniques have been used to identify and localize ion transport pathways along the d istal tubule and to identify human diseases that result from abnormal dista l tubule function. Results of these studies have clarified the roles of ind ividual distal cell types. They suggest that the basic molecular architectu re of the distal nephron is surprisingly similar in mammalian species inves tigated to date. The results have also reemphasized the role played by the distal tubule in regulating urinary potassium excretion. They have clarifie d how both peptide and steroid hormones, including aldosterone and estrogen , regulate ion transport by distal convoluted tubule cells. Furthermore, th ey highlight the central role that the distal tubule plays in systemic calc ium homeostasis. Disorders of distal nephron function, such as Gitelman's s yndrome, nephrolithiasis, and adaptation to diuretic drug administration, e mphasize the importance of this relatively short nephron segment to human p hysiology. This review integrates molecular and functional results to provi de a contemporary picture of distal tubule function in mammals.