H+/K+-ATPase pump
The H+/K+-ATPase pump or proton pump is a magnesium-dependant enzyme which causes the exchange of a proton against a potassium ion through a membrane. This pump is present in the colon, the kidney, but especially the stomach where it is particularly active.
In the stomach, this pump causes the secretion of protons into the gastric fluid which becomes acid. It generates a gradient of pH of more than 6 units: whereas the blood pH is 7.3 that of the gastric fluid is about 1.
The proton pump is located at the apical pole, i.e. luminal, of the parietal cells of the gastric mucosa. It consists of an alpha subunit responsible of pumping and hydrolysis of ATP and a beta subunit whose function is poorly understood.
In the non secreting state, the H+/K+-ATPase pump is contained in a vesicle inside the cytoplasm of the parietal cells. During its activation, it migrates to fit in plasma membrane in transmembrane position, outside in contact with the gastric fluid which contains potassium. It exchanges a potassium ion against a proton in an electroneutral way, i.e. without modification of cellular polarization. Energy required for the exchange is provided by the hydrolysis of the ATP regenerated by mitochondria.
Secretion of HCl by the gastric parietal cell
(R = receptors, PKa = protein kinase)
The Cl- secretion is probably coupled with that of K+ which is recycled.
The principal stimulant of the H+/K+-ATPase pump is food intake which acts by release of histamine, gastrin and acetylcholine, which activate, via the cAMP or calcium, protein kinases which, themselves, activate the H+/K+-ATPase.
Gastrin is a heptadecapeptide secreted by the pyloric antrum under the influence of vagal stimulation and intake of food. It stimulates secretion by the gastric mucosa of protons, pepsin and the intrinsic factor. It stimulates also pancreatic secretion, and inhibits the electrolyte and water reabsorption by the intestine, which can induce diarrhea. It relaxes the Oddi sphincter and slows gastric emptying. When it is given in the form of pentagastrin to explore the gastric secretion, it can give nausea and an increase of intestinal peristalsis.
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