Na–K–Cl cotransporter
solute carrier family 12 member 1 | |||||||
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Identifiers | |||||||
Symbol | SLC12A1 | ||||||
Alt. symbols | NKCC2 | ||||||
Chr. 15 q21.1 | |||||||
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solute carrier family 12 member 2 | |||||||
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Identifiers | |||||||
Symbol | SLC12A2 | ||||||
Alt. symbols | NKCC1 | ||||||
Chr. 5 q23.3 | |||||||
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The Na–K–Cl
NKCC1 is widely distributed throughout the human body; it has important functions in
Function
NKCC proteins are membrane transport proteins that transport sodium (Na), potassium (K), and chloride (Cl) ions across the cell membrane. Because they move each solute in the same direction, they are considered symporters. They maintain electroneutrality by moving two positively charged solutes (sodium and potassium) alongside two parts of a negatively charged solute (chloride). Thus the stoichiometry of the transported solutes is 1Na:1K:2Cl. However, there is a notable exception in squid giant axon as the symporter in this special cell has a stoichiometry of 2Na:1K:3Cl, although electroneutrality is still maintained.[3]
NKCC1
NKCC1 is widely distributed throughout the body, especially in organs that
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. Inhibition of NKCC1, as with furosemide or other loop diuretics, can result in deafness.[5]
NKCC1 is also expressed in many regions of the
NKCC2
NKCC2 is specifically found in cells of the
The thick ascending limb of the loop of Henle begins at the deeper portion of the renal outer medulla. Here, the urine has a relatively high concentration of sodium. As urine moves towards the more superficial portion of the thick ascending limb, NKCC2 is the major transport protein by which sodium is reabsorbed from the urine. This outward movement of sodium and the lack of water permeability in the thick ascending limb, creates a more diluted urine.[9] According to the stoichiometry outlined above, each sodium ion reabsorbed brings one potassium ion and two chloride ions. Sodium goes on to be reabsorbed into the blood, where it contributes to the maintenance of blood pressure.
Furosemide and other loop diuretics inhibit the activity of NKCC2, thereby impairing sodium reabsorption in the thick ascending limb of the loop of Henle. The action of these loop diuretics also reduces potassium reabsorption through the NKCC2 cotransporter and consequently increases tubular flow rate which enhances potassium secretion and emphasises the hypokalaemic effect.
Impaired sodium reabsorption increases diuresis by three mechanisms:
- Increases the amount of active osmolytes in urine by decreasing absorption of sodium
- Erases the papillar gradient
- Inhibits tubuloglomerular feedback
Loop diuretics therefore ultimately result in decreased blood pressure.
The hormone
Genetics
NKCC1 and NKCC2 are encoded by genes on the long arms of chromosomes 5[12] and 15,[13] 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.[13]
Kinetics
The
See also
- Cotransport
- Cotransporter
References
External links
- Sodium-Potassium-Chloride+Symporters at the U.S. National Library of Medicine Medical Subject Headings (MeSH)