Editing Sodium–potassium pump (section)

=== Exogenous ===
The {{chem2|Na+/K+}}-ATPase can be pharmacologically modified by administering drugs exogenously. Its expression can also be modified through hormones such as [[triiodothyronine]], a [[thyroid]] hormone.{{r|Ramnanan}}<ref>{{Cite journal| vauthors = Lin HH, Tang MJ |date= January 1997|title=Thyroid hormone upregulates Na,K-ATPase α and β mRNA in primary cultures of proximal tubule cells |journal=Life Sciences |volume=60 |issue=6 |pages=375–382 |doi=10.1016/S0024-3205(96)00661-3 |pmid= 9031683}}</ref>

For instance, {{chem2|Na+/K+}}-ATPase found in the membrane of heart cells is an important target of [[cardiac glycoside]]s (for example [[digoxin]] and [[ouabain]]), [[inotrope|inotropic]] drugs used to improve [[heart]] performance by increasing its force of contraction.

Muscle contraction is dependent on a 100- to 10,000-times-higher-than-resting intracellular [[Calcium in biology|{{chem2|Ca^{2+}|}}]] concentration, which is caused by {{chem2|Ca^{2+}|}} release from the muscle cells' sarcoplasmic reticulum. Immediately after muscle contraction, intracellular {{chem2|Ca^{2+}|}} is quickly returned to its normal concentration by a carrier enzyme in the plasma membrane, and a calcium pump in [[sarcoplasmic reticulum]], causing the muscle to relax.

According to the Blaustein-hypothesis,<ref name="pmid324293">{{cite journal | vauthors = Blaustein MP | s2cid = 9814212 | title = Sodium ions, calcium ions, blood pressure regulation, and hypertension: a reassessment and a hypothesis | journal = The American Journal of Physiology | volume = 232 | issue = 5 | pages = C165-73 | date = May 1977 | pmid = 324293 | doi = 10.1152/ajpcell.1977.232.5.C165 }}</ref> this carrier enzyme ({{chem2|Na+/Ca^{2+}|}} exchanger, NCX) uses the Na gradient generated by the {{chem2|Na+}}-{{chem2|K+}} pump to remove {{chem2|Ca^{2+}|}} from the intracellular space, hence slowing down the {{chem2|Na+}}-{{chem2|K+}} pump results in a permanently elevated {{chem2|Ca^{2+}|}} level in the [[muscle]], which may be the mechanism of the long-term inotropic effect of cardiac glycosides such as digoxin. The problem with this hypothesis is that at pharmacological concentrations of digitalis, less than 5% of Na/K-ATPase molecules – specifically the α2 isoform in heart and arterial smooth muscle (''K''<sub>d</sub> = 32 nM) – are inhibited, not enough to affect the intracellular concentration of {{chem2|Na+}}. However, apart from the population of Na/K-ATPase in the plasma membrane, responsible for ion transport, there is another population in the [[caveolae]] which acts as digitalis receptor and stimulates the [[EGF receptor]].<ref name="pmid18556748">{{cite journal | vauthors = Schoner W, Scheiner-Bobis G | title = Role of endogenous cardiotonic steroids in sodium homeostasis | journal = Nephrology, Dialysis, Transplantation | volume = 23 | issue = 9 | pages = 2723–9 | date = September 2008 | pmid = 18556748 | doi = 10.1093/ndt/gfn325 | doi-access =  }}</ref><ref name="pmid20211726">{{cite journal | vauthors = Blaustein MP, Hamlyn JM | title = Signaling mechanisms that link salt retention to hypertension: endogenous ouabain, the Na<sup>+</sup> pump, the Na<sup>+</sup>/Ca<sup>2+</sup> exchanger and TRPC proteins | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1802 | issue = 12 | pages = 1219–29 | date = December 2010 | pmid = 20211726 | pmc = 2909369 | doi = 10.1016/j.bbadis.2010.02.011 }}</ref><ref name="pmid21642827">{{cite journal | vauthors = Fuerstenwerth H | s2cid = 20180376 | title = On the differences between ouabain and digitalis glycosides | journal = American Journal of Therapeutics | volume = 21 | issue = 1 | pages = 35–42 | date = 2014 | pmid = 21642827 | doi = 10.1097/MJT.0b013e318217a609 }}</ref><ref name="pmid25341357">{{cite journal | vauthors = Pavlovic D | title = The role of cardiotonic steroids in the pathogenesis of cardiomyopathy in chronic kidney disease | journal = Nephron Clinical Practice | volume = 128 | issue = 1–2 | pages = 11–21 | date = 2014 | pmid = 25341357 | doi = 10.1159/000363301 | s2cid = 2066801 | doi-access =  }}</ref>