Sodium entry pathways in renal epithelial cell lines

Abstract

Na+ entry into kidney epithelial cells occurs by a multiplicity of pathways. Established cell lines such as the A6 cells, derived from the collecting duct of the kidney of Xenopus laevis, MDCK cells, from the distal tubule of a dog kidney, and the LLC-PK1 cells, originating from the proximal tubule of a pig kidney, provide excellent model cell systems for the detailed characterization and isolation of the proteins which comprise these entry pathways. Major pathways of Na+ entry include the amiloride-sensitive Na+ channel, the amiloride-sensitive Na+/H+ antiporter, and the loop diuretic-sensitive NaCl/KCl symporter. While the former two systems have been shown to exhibit an apical location in epithelial cells so far examined, the last system may be localized to either the basolateral or apical surface, depending on the transport function of the cell. Nutrient/Na+ symporters such as the glucose, phosphate, and p-aminohippurate symporters may all be localized to the apical surfaces of proximal tubular cells, but other systems, including those specific for neutral amino acids, may predominate in the basolateral surface or be distributed between the two membranes. Studies concerned with the catalytic, structural, and regulatory properties of these transport systems serve not only to characterize the individual translocators in established cell lines, but also to suggest their physiological functions in intact kidney tissues.