Na–K–Cl cotransporter

In contrast, NKCC2 is found specifically in the kidney, where it extracts sodium, potassium, and chloride from the urine so they can be reabsorbed into the blood.

Its basolateral location gives NKCC1 the ability to transport sodium, potassium, and chloride from the blood into the cell.

In addition to exocrine glands, NKCC1 is necessary for establishing the potassium-rich endolymph that bathes part of the cochlea, an organ necessary for hearing.

[10] Additionally, NKCC1 is present in the dark cells of the vestibule and contributes to generation of the endolymph of the vestibular system.

[14] The mechanism behind NKCC1-dependent male fertility is unclear, it is possible that the observed decreased sperm count could be due to either lack of NKCC1 cotransport in the testis or upstream failure of NKCC1-expressing neurons in the hypothalamus to release gonadotropin-releasing hormone.

[15] NKCC2 is specifically found in cells of the thick ascending limb of the loop of Henle and the macula densa in nephrons, the basic functional units of the kidney.

The thick ascending limb of the loop of Henle begins at the deeper portion of the renal outer medulla.

This outward movement of sodium and the lack of water permeability in the thick ascending limb, creates a more diluted urine.

Impaired sodium reabsorption increases diuresis by three mechanisms: Loop diuretics therefore ultimately result in decreased blood pressure.

Vasopressin stimulates sodium chloride reabsorption in the thick ascending limb of the nephron by activating signaling pathways.

Increased NKCC2 activity aids in water reabsorption in the collecting duct through aquaporin 2 channels by creating a hypo-osmotic filtrate.

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.

[20] The promotor for gene SLC12A2, which encodes for NKCC1, contains binding sites for homeobox transcription factors SIX1 and SIX4, which have been shown to upregulate NKCC1 mRNA expression when bound.

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.