Na+-K+-2Cl− Cotransporter

Abstract

The conceptual breakthrough that the energy of the Na+ gradient gener- ated by the Na+/K+ pump could be used as the driving force for another membrane transport protein has led to the functional and molecular identification of multiple secondary active transporters. We have organized this chapter to address the expression, function, regulation, and evolutionary importance of the two isoforms of the electroneutral sodium-potassium-chloride cotransporter (NKCC). The combi- nation of basolateral expression of the sodium-potassium pump and NKCC1 in various epithelia results in salt and water secretion, whereas basolateral expression of the pump with apical expression of NKCC2 in the thick ascending limb of Henle in the kidney nephron results in salt and water reabsorption. NKCCs are regulated by serine-threonine phosphorylation of specific residues in their amino-terminal domain, and the evolutionary conservation of these cotransporters from protists to humans confirms their vital role in cellular and whole-organism physiology/