Proton secretion by the gastric parietal cell.

The parietal cell occupies a unique niche among eukaryotic cells in that it develops a proton gradient of more than 4 million-fold across the membrane of the secretory canaliculus. At rest, the cell is still able to develop a proton gradient across intracellular membranes, such that the acid compartment has a pH of less than 4. Acidification depends on the simultaneous presence of ATP, K+ and Cl- as demonstrated in permeabilized cells. With acidification of the luminal side of the proton pump, there is a corresponding alkalinization of the cytosolic face as revealed by carboxyfluorescein fluorescence enhancement. Disposal of the resultant alkali depends on carbonic anhydrase activity and the functioning of a coupled Na+:H+ and Cl-:OH-antiport across the basal lateral membrane. Accordingly, with secretion there is an increased cellular Cl- level, which is exported across the apical membrane in association with K+. The Na+ pump dependent secretion of KCl across this membrane is one of the major sites of the gastric ATPase. Membranes isolated from secreting tissue contain a KCl permeation pathway largely absent from membranes isolated from resting tissue. The pump itself acts as an H+ for K+ exchange ATPase which is most probably composed of at least two peptides of 100 000 Mr. That catalytic cycle consists of formation and breakdown of a covalent aspartyl phosphate. Formation of the intermediate depends on loss of K+ from cytosolic binding sites, and breakdown of the intermediate depends on K+ binding to the luminal face of the enzyme. During breakdown, an acid labile E . P is formed, and, at high ATP concentrations, loss of this form of the enzyme is probably the rate limiting step.