NKCC2 (source code)
= NKCC2
{c}
\b[NKCC2] is the kidney-enriched sodium–potassium–chloride <cotransporter> that carries one $\mathrm{Na^+}$, one $\mathrm{K^+}$ and two $\mathrm{Cl^-}$ 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.<Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney by G. Gamba and others>[Kidney transporter cloning, functional expression and intrarenal localization; distinction from the Na-Cl transporter.]{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 is
$$
\Delta G=RT\ln(r_{\mathrm{Na}}r_{\mathrm K}r_{\mathrm{Cl}}^2).
$$
The 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.<Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney by G. Gamba and others>[Abstract: functional characterization in oocytes, inhibitor sensitivity and approximately 60% sequence similarity of the two cloned transporters.]{ref}
Back to article page
