 NKCC2

NKCC2 is the kidney-enriched sodium–potassium–chloride cotransporter that carries one $\mathrm{N}{\mathrm{a}}^{+}$, one ${\mathrm{K}}^{+}$ and two $\mathrm{C}{\mathrm{l}}^{-}$ ions together across a biological membrane in each coupled transport cycle. In the thick ascending limb of the Loop of Henle, NKCC2 supports salt uptake from the tubular lumen. It is a secondary active transport system: the coupled ion gradients provide the immediate driving force, while the sodium-potassium ATPase helps maintain those gradients.^[ref]

The stoichiometry explains why transport is electrically silent: one cycle moves net charge $1+1-2=0$. This does not mean no ions move or no energy is involved. If $r_j$ is the activity inside divided by activity outside for ion $j$, the idealized free-energy change for inward transport isThe membrane-potential contributions cancel because the coupled net charge is zero. A favorable sodium ratio can therefore help drive other ions uphill in their chemical gradients. This expression assumes tightly coupled transport with the stated stoichiometry.

The molecular identification combined cloning with a functional assay: investigators expressed the kidney transporter in Xenopus oocytes and tested ion transport and inhibition by bumetanide. Comparison with a related thiazide-sensitive sodium–chloride transporter separated similar-looking sequences by their potassium requirement and drug sensitivity. The experiment illustrates why sequence similarity alone does not establish identical transport function.^[ref]