Na+/K+ ATPase

Na+/K+-ATPase (sodium-potassium adenosine triphosphatase, also known as the Na+/K+ pump or sodium-potassium pump) is an enzyme (an electrogenic transmembrane ATPase) found in the plasma membrane of all animal cells. The Na+/K+-ATPase enzyme is a solute pump that pumps sodium out of cells while pumping potassium into cells, both against their concentration gradients. This pumping is active and is important for cell physiology. An example application is nerve conduction.

Ursolic acid


An overview of Na+/K+ ATPase

Na+/K+ ATPase (NKA), the sodium pump, was inadvertently discovered by Jens who was awarded the Nobel Prize for the researches on NKA in 1997. NKA, membrane-bound enzymes, exerts its function by translocating Na+ and K+across the cell membrane at the cost of ATP. In this process, when three Na+ are extruded, two K+ are imported, which is derived by hydrolyzing ATP. NKA is widely expressed in eukaryotic cells, providing the diffusion gradient of Na+ and K+ to maintain the resting membrane potential. NKA consists of three subunits: α, β and γ subunits. While catalytic α-subunits provide the binding sites for ATP, Na+, K+, and the inhibitor cardiotonic steroids, β-subunits regulate the stability and activation ofα-subunits.

Inhibition of Na+/K+ATPase

Cardiotonic steroids are able to specifically inhibit the activity of NKA. Cardiotonic steroids are used as therapeutic in many diseases, including congestive heart failure, cardiac arrhythmias and human cancers. Recent experiments have demonstrated that the NKA inhibitor cardiotonic steroids could induce anti-cancer effects attributed to their potent antiproliferative effects on cancer cells. Quabain and digoxin are representative cardiotonic steroids, and play a crucial role in the treatment of congestive heart failure and CHIKV infection, respectively. Suloctidil is a new drug that is currently being evaluated in many clinical trials for the treatment of dementia and thrombosis. Suloctidil acts on brain synapses in rats and affects the activity of NKA.

Na+/K+ ATPase and diseases

NKA is expressed in various cells and tissues with pathophysiological functions. The overexpression of NKA is found in congestive heart failure and hypertension. It is confirmed that NKA is expressed in renal and changes in NKA activation may lead to early renal hypertrophy. NKA has positive effect in nervous system against neurodegenerative disorders like Alzheimer’s disease. It is believed that NKA is involved in cancers and the expression of NKA is regarded as a biomarker of a therapeutic response in cancer chemotherapy.


1. Zhang, L. N., Sun, Y. J., Pan, S., Li, J. X., Qu, Y. E., Li, Y & Gao, Z. B. (2013). Na+‐K+‐ATP ase, a potent neuroprotective modulator against A lzheimer disease. Fundamental & clinical pharmacology, 27(1), 96-103.

2. Mijatovic, T., Dufrasne, F., & Kiss, R. (2012). Na+/K+-ATPase and cancer. Pharmaceutical patent analyst, 1(1), 91-106.

3. Vagin, O., Dada, L. A., Tokhtaeva, E., & Sachs, G. (2012). The Na-K-ATPase α1β1 heterodimer as a cell adhesion molecule in epithelia. American Journal of Physiology-Cell Physiology, 302(9), C1271-C1281.