The H⁺/K⁺ ATPase is a heterodimeric protein, made up of α and β subunits. The α subunit has 10 TM domains and exhibits catalytic and pore functions, while the β subunit has a single TM domain, which appears to be required for intracellular trafficking and stabilising the α subunit. The ATP4A and ATP4B subunits are expressed together, while the ATP12A subunit is suggested to be expressed with the β1 (ATP1B1) subunit of the Na⁺/K⁺-ATPase [1].

The gastric H⁺/K⁺-ATPase is inhibited by proton pump inhibitors (PPIs, e.g. dexlansoprazole and esomeprazole) which are used to treat excessive gastric acid secretion. PPIs have a gradual onset of action. More quickly acting potassium-competitive acid blockers (P-CABs; e.g. vonoprazan, revaprazan and tegoprazan) have now entered the clinic. P-CABs are competitive and reversible H⁺/K⁺ ATPase blockers and their effect on acid suppression is stronger and more sustained compared to PPIs.

* Key recommended reading is highlighted with an asterisk

* Tanaka S, Morita M, Yamagishi T, Madapally HV, Hayashida K, Khandelia H, Gerle C, Shigematsu H, Oshima A, Abe K. (2022) Structural Basis for Binding of Potassium-Competitive Acid Blockers to the Gastric Proton Pump. J Med Chem, [Epub ahead of print]. [PMID:35604136]

1. Pestov NB, Korneenko TV, Shakhparonov MI, Shull GE, Modyanov NN. (2006) Loss of acidification of anterior prostate fluids in Atp12a-null mutant mice indicates that nongastric H-K-ATPase functions as proton pump in vivo. Am J Physiol, Cell Physiol, 291 (2): C366-74. [PMID:16525125]