Na-K-Cl cotransport in chloride-transporting epithelia

The elasmobranch rectal gland has served as a useful model to study features of Na-K-Cl cotransport that are common to many chloride-transporting epithelia. These include: (1) dependence on a Na+ gradient created by Na-K-ATPase; (2) high intracellular Cl- concentration; (3) characteristic inhibitor profile including inhibition by loop diuretics and barium but not by amiloride, SITS, DIDS, or carbonic anhydrase inhibitors; and (4) remarkable energy efficiency of transepithelial transport (25-30 NaCl/l 02). The mechanism by which this is accomplished is clarified by kinetic analysis of experiments with isolated perfused rectal glands of Squalus acanthias in which perfusate concentrations of Na and Cl are systematically varied. These show a Hill coefficient of one for Na+ and two for Cl-, suggesting that one Na+, one K+, and two Cl- interact with the cotransport carrier. Nitrate can substitute for Cl- to some extent, and it itself weakly transported. The loop diuretic bumetanide behaves like a competitive inhibitor of Cl-. The teleological significance of the neutral cotransport of two Cl- with one Na+ and one K+ is that it enables transporting epithelia like the rectal gland, cornea, salivary gland, and thick ascending limb of Henle's loop to double the efficiency of their Na-K-ATPase pump.