The Na-K-Cl cotransporters are a class of membrane proteins that transport Na⁺, K⁺, and Cl^- ions into and out of cells in an electrically neutral manner, in most cases with a stoichiometry of 1Na⁺:1K⁺:2Cl^-. Na-K-Cl cotransporters are present in a wide variety of cells and tissues, including reabsorptive and secretory epithelia, nerve and muscle cells, endothelial cells, fibroblasts, and blood cells.

Na-K-Cl cotransport plays a vital role in renal salt reabsorption and in salt secretion by intestinal, airway, salivary gland, and other secretory epithelia.¹ Na-K-Cl cotransport activity is inhibited by "loop" diuretics, including the clinically efficacious agents, bumetanide and furosemide. The regulation of Na-K-Cl cotransport is mediated, at least in some cases, through direct phosphorylation of the cotransport protein.²

NKCC1 is one of two Na-K-Cl cotransporter isoforms that have been identified. NKCC1 is present in a wide variety of secretory epithelia and non-epithelial cells.³ NKCC1 is expressed in virtually all mammalian cells and is thought to play a housekeeping role in cell volume homeostasis and the common control of cytosolic ion content. NKCC1 does not use ATP but operates using electrochemical gradient for Na⁺ and K⁺ produced by Na⁺-K⁺-ATPase.⁴ There is considerable evidence that uptake of Cl⁻ in immature neurons is mediated by NKCC1. High expression of NKCC1 in immature neurons plays an important role in maintaining high intracellular Cl⁻.⁵