NKCC2 to the membrane and phosphorylates some serine and threonine sites on the cytoplasmic N-terminal of the NKCC2 located in the membrane, increasing its activity. Increased NKCC2 activity aids in water reabsorption in the collecting duct through aquaporin 2 channels by creating a hypo-osmotic filtrate. Genetics NKCC1 and NKCC2 are encoded by genes on the long arms of chromosomes 5 and 15, respectively. A loss of function mutation of NKCC2 produces Bartter syndrome, an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis with normal to low blood pressure. Kinetics The energy required to move solutes across the cell membrane is provided by the electrochemical gradient of sodium. Sodium's electrochemical gradient is established by the Na-K ATPase, which is an ATP-dependent enzyme. Since NKCC proteins use sodium's gradient, their activity is indirectly dependent on ATP; for this reason, NKCC proteins are said to move solutes by way of secondary active transport. There are three isoforms of NKCC2 created by alternative splicing (NKCC2A, B and F). Each one of these isoforms is expressed at different portions of the thick ascending limb and they have different affinity for sodium that correlates with its localization. The isoform F is more predominant in the deeper portion of the thick ascending limb, where the sodium concentration is very high. NKCC2F is the isoform with the lowest affinity for sodium and this allows the cotransporter to work at this sodium rich environment. Conversely, NKCC2B is expressed at the more superficial portion of the thick ascending limb and the macula densa, and it has the highest affinity for sodium. This permits NKCC2B to function in this sodium-depleted environment without saturating. The NKCC2A isoform shows an intermediate distribution and affinity for sodium. In this way, NKCC2 is able to function properly along the range of sodium concentrations found along the thick ascending limb. See also Cotransport Cotransporter References External links Solute carrier family