Editing Sodium–potassium pump (section)

=== Endogenous ===
The {{chem2|Na+/K+}}-ATPase is upregulated by [[Cyclic adenosine monophosphate|cAMP]].<ref>{{cite book | vauthors = Burnier M |title=Sodium In Health And Disease |url=https://books.google.com/books?id=RZK8c6eV76MC&pg=PA15 |year=2008 |publisher=CRC Press |isbn=978-0-8493-3978-3 |page=15}}</ref> Thus, substances causing an increase in cAMP upregulate the {{chem2|Na+/K+}}-ATPase. These include the ligands of the [[Gs alpha subunit|G<sub>s</sub>]]-coupled GPCRs. In contrast, substances causing a decrease in cAMP downregulate the {{chem2|Na+/K+}}-ATPase. These include the ligands of the [[Gi alpha subunit|G<sub>i</sub>]]-coupled GPCRs. Note: Early studies indicated the ''opposite'' effect, but these were later found to be inaccurate due to additional complicating factors. {{Citation needed|date=February 2010}}

The {{chem2|Na+/K+}}-ATPase is endogenously negatively regulated by the inositol pyrophosphate 5-InsP7, an intracellular signaling molecule generated by [[IHPK1|IP6K1]], which relieves an autoinhibitory domain of [[Phosphoinositide 3-kinase|PI3K]] [[PIK3R1|p85α]] to drive endocytosis and degradation.<ref>{{cite journal | vauthors = Chin AC, Gao Z, Riley AM, Furkert D, Wittwer C, Dutta A, Rojas T, Semenza ER, Felder RA, Pluznick JL, Jessen HJ, Fiedler D, Potter BV, Snyder SH, Fu C | display-authors = 6 | title = The inositol pyrophosphate 5-InsP<sub>7</sub> drives sodium-potassium pump degradation by relieving an autoinhibitory domain of PI3K p85α | journal = Science Advances | volume = 6 | issue = 44 | page = eabb8542 | date = October 2020 | pmid = 33115740 | pmc = 7608788 | doi = 10.1126/sciadv.abb8542 | s2cid = 226036261 | bibcode = 2020SciA....6.8542C }}</ref>

The {{chem2|Na+/K+}}-ATPase is also regulated by reversible phosphorylation. Research has shown that in estivating animals, the {{chem2|Na+/K+}}-ATPase is in the phosphorylated and low activity form. Dephosphorylation of {{chem2|Na+/K+}}-ATPase can recover it to the high activity form.{{r|Ramnanan}}