The Cell Biology of Gastric Acid Secretion

The regulation of gastric HCl secretion by the parietal cell occurs primarily through the regulated recycling of H,K-ATPase. Secretagogue stimulation of the parietal cell initiates HCl secretion by effecting an intracellular signaling and biochemical pathway that culminates with the membrane fusion of intracellular H,K-ATPase-rich tubulovesicles with, and thus, the delivery of the H,K-ATPase to the secretory canaliculus (apical membrane). On withdrawal of the secretagogue, cessation of secretion occurs concomitantly with the retrieval of the H,K-ATPase from the secretory canaliculus, and the reformation of the tubulovesicular membrane compartment. The H,K-ATPase resides quiescently in this compartment until another round of secretion is initiated. Intracellular signaling pathways, cytoskeletal elements, and vesicular trafficking machinery must be coordinately regulated to effect this membrane-recycling pathway. This chapter summarizes key findings from experimental approaches taken toward the elucidation of the mechanism of gastric HCl secretion, through the use of electron microscopy, electrophysiology, membrane biochemistry, molecular biology, cell biology, and atomic structure, in the characterization of the regulation of activity of the H,K-ATPase itself, to that of associated ion channels and membrane transporters, as well as of the regulation of H,K-ATPase trafficking.