Properties and Diversity of (Na-K-C1) Cotransporters

Abstract

A specific pathway that mediates the coupled, electrically neutral transport of Na, K, and Cl ions across cell membranes is present in a wide variety of animal tissues, and appears to serve a number of different physiological functions. (Na-K-Cl) cotransport is involved in transport of salt and water across both reabsorptive and secretory epithelia, including the thick ascending limb of Henle's loop (TALH) of mammalian kidney (33), distal tubule of amphibian kidney (67), Necturus gallbladder (12), shark rectal gland (46), rabbit parotid (91), and flounder intestine (72, 73). In other cells, including Ehrlich ascites tumor cells (30, 31) and human red blood cells (17), (Na-K­ Cl) cotransport may play a role in the maintenance and regulation of cell volume. In excitable cells, such as squid axon (4, 85) and cardiac myocytes (57), this cotransporter may regulate the ion gradients that determine the resting membrane potential, and recent evidence suggests that the cotransport system of chick cardiac myocytes is stimulated by catecholamines, which enhance cardiac contractility (57). In avian red cells, (Na-K-Cl) cotransport is also stimulated by ,B-adrenergic catecholamines (44, 89, 92), and the high rate of cotransport in these cells may contribute to extrarenal potassium regulation in birds (43). Reduced levels of (Na-K-Cl) cotransport in vascular smooth muscle cells may reflect or even contribute to the pathogenesis of essential hypertension (71). As we continue to find (Na-K-Cl) cotransport in an increasing number of tissues, this pathway will likely be found to serve still other physiological functions, and abnormalities in its operation or regulation may prove to be important in the pathophysiology of specific disease states. In this review, we compare properties of (Na-K-CI) cotransport systems