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Flow of ions.

Alpha and beta units.

Sodium-potassium pump, E2-Pi state. Calculated hydrocarbon boundaries of the lipid bilayer are shown as blue (intracellular) and red (extracellular) planes

Na⁺/K⁺-ATPase (also known as the Na⁺/K⁺ pump, sodium-potassium pump, or simply NAKA, for short) is an enzyme (EC 3.6.3.9) located in the plasma membrane (specifically an electrogenic transmembrane ATPase). It is found in the plasma membrane of virtually every human cell and is common to all cellular life.

The Na⁺/K⁺-ATPase helps maintain resting potential, avail transport and regulate cellular volume.

See also: Resting potential

In order to maintain the cell potential, cells must keep a low concentration of sodium ions and high levels of potassium ions within the cell (intracellular). Outside cells (extracellular), there are high concentrations of sodium and low concentrations of potassium, so diffusion occurs through ion channels in the plasma membrane. In order to keep the appropriate concentrations, the sodium-potassium pump pumps sodium out and potassium in through active transport. As the plasma membrane is far less permeable to sodium than it is to potassium ions, an electric potential (negative intracellularly) is the eventual result.

The resting potential avails action potentials of nerves and muscles.

Export of sodium from the cell provides the driving force for several facilitated membrane transport proteins, which import glucose, amino acids and other nutrients into the cell. Translocation of sodium from one side of an epithelium to the other side creates an osmotic gradient that drives the absorption of water.

Another important task of the Na⁺-K⁺ pump is to provide a Na⁺ gradient that is used by certain carrier processes. In the gut, for example, sodium is transported out of the resorbing cell on the blood side via the Na⁺-K⁺ pump, whereas, on the resorbing side, the Na⁺-Glucose symporter uses the created Na⁺ gradient as a source of energy to import both Na⁺ and Glucose, which is far more efficient than simple diffusion. Similar processes are located in the renal tubular system.

• The pump, with bound ATP, binds 3 intracellular Na⁺ ions.
• ATP is hydrolyzed, leading to phosphorylation of the pump at a highly conserved aspartate residue and subsequent release of ADP.
• A conformational change in the pump exposes the Na⁺ ions to the outside. The phosphorylated form of the pump has a low affinity for Na⁺ ions, so they are released.
• The pump binds 2 extracellular K⁺ ions. This causes the dephosphorylation of the pump, reverting it to its previous conformational state, transporting the K⁺ ions into the cell.
• The unphosphorylated form of the pump has a higher affinity for Na⁺ ions than K⁺ ions, so the two bound K⁺ ions are released. ATP binds, and the process starts again.

The Na⁺/K⁺-ATPase is thought to be downregulated by cAMP ^[1].

Thus, substances causing an increase in cAMP downregulates Na⁺/K⁺-ATPase. These include the ligands of the G_s-coupled GPCRs.

In contrast, substances causing a decrease in cAMP upregulates Na⁺/K⁺-ATPase. These include the ligands of the G_i-coupled GPCRs.

The Na⁺-K⁺-ATPase can be pharmacologically modified by administrating drugs exogenously.

For instance, Na⁺-K⁺-ATPase found in the membrane of heart cells is an important target of cardiac glycosides (for example digoxin and ouabain), inotropic drugs used to improve heart performance by increasing its force of contraction.

Contraction of any muscle is dependent on a 100- to 10,000-times higher-than-resting intracellular Ca²⁺ concentration, which, as soon as it is put back again on its normal level by a carrier enzyme in the plasma membrane, and a calcium pump in sarcoplasmic reticulum, muscle relaxes.

Since this carrier enzyme (Na⁺-Ca²⁺ translocator) uses the Na gradient generated by the Na⁺-K⁺ pump to remove Ca²⁺ from the intracellular space, slowing down the Na⁺-K⁺ pump results in a permanently-higher Ca²⁺ level in the muscle, which will eventually lead to stronger contractions.

Na⁺/K⁺-ATPase was discovered by Jens Christian Skou in 1957 while working as assistant professor at the Department of Physiology, University of Aarhus, Denmark. He published his work in 1957.^[2]

In 1997, he received one-half of the Nobel Prize in Chemistry "for the first discovery of an ion-transporting enzyme, Na⁺, K⁺ -ATPase."^[3]

• Alpha: ATP1A1, ATP1A2, ATP1A3, ATP1A4. #1 predominates in kidney. #2 is also known as "alpha(+)"
• Beta: ATP1B1, ATP1B2, ATP1B3, ATP1B4

• V-ATPase
• active transport

1. ^ Regulation of Na+-K+-ATPase by cAMP-dependent protein kinase anchored on membrane via its anchoring protein Kinji Kurihara, Nobuo Nakanishi, and Takao Ueha. Departments of 1 Oral Physiology and 2 Biochemistry, School of Dentistry, Meikai University, Sakado, Saitama 350-0283, Japan
2. ^ Skou J (1957). "The influence of some cations on an adenosine triphosphatase from peripheral nerves.". Biochim Biophys Acta 23 (2): 394-401. PMID 13412736. 
3. ^ http://nobelprize.org/chemistry/laureates/1997/index.html

A pdf copy of the paper (reference 1) appears on http://jasn.asnjournals.org/cgi/reprint/9/11/2170.pdf

• MeSH Sodium,+Potassium+ATPase