The gastric H+,K(+)-ATPase

Mammalian extramitochondrial pumps can be divided into two different classes: the vacuolar H(+)-ATPases, which are responsible for acidification of intracellular compartments, and the E1E2-type of ATPases, which are represented by the Na+,K(+)-ATPase, the Ca2(+)-ATPase and the gastric H+,K(+)-ATPase. The latter enzyme is confined to the tubulovesicles and to the secretory membranes of the parietal cell and has been shown to be the proton pump of the gastric mucosa. The H+,K(+)-ATPase carries out the electroneutral exchange of H+ and K+ and thereby generates a pH of less than 1 in the secretory canaliculus. For this process to occur, the enzyme must be activated by extracytosolic potassium ions. These ions reach the parietal cell luminal space by a secretagogue-induced stimulation of a KCl pathway in the secretory membrane of the parietal cell. Kinetic studies in isolated ion-tight and ion-permeable gastric vesicles have shown that intravesicular K+ stimulates the ATPase activity and accelerates the breakdown of the phosphorylenzyme intermediate formed during the catalytic cycle of the H+,K(+)-ATPase. Thus the stimulation of the ATPase activity by K+ is due to an increased rate of hydrolysis of phosphoenzyme. When the ATPase activity was analysed in permeable vesicles and at high K+ concentrations, the ATPase activity was inhibited. In contrast, when the overall ATPase activity was analysed in ion-tight vesicles, which developed an intravesicular positive potential in the presence of valinomycin, no inhibition of the ATPase activity was observed.(ABSTRACT TRUNCATED AT 250 WORDS)