Acid is secreted by the gastric gland parietal cells via the action of the gastric H+/K+ ATPase, a transmembrane proton pump. In nonstimulated parietal cells the pump is present in cytoplasmic vesicles (the tubulovesicles) separated from the apical membrane. Electron microscopy studies have shown that these vesicles are in fact small stacks of cisternae and should be called tubulocisternae. On stimulation the pumps are transported in vesicles to the apical membrane along the actin cytoskeleton where they fuse to and greatly increase the surface area of the apical membrane forming numerous microvilli. When physiological stimuli for acid secretion is removed the pumps are recycled back to the tubulo-cisternae. These trafficking processes involve: (1) movement to the apical membrane of vesicles containing the H+/K+ATPase; (2) fusion with the apical membrane and formation of actin filament-based scaffolds to form surface microvilli; (3) dissolution of the actin scaffolds; and (4) transport of the endo-cytotic vesicles containing the H+/K+ATPase back to the tubulocisternae. Numerous proteins have been reported to be associated with these processes; rab11 (a GTPase), syntaxin 3, VAMPs (vesicle associated membrane protein), c-src (a nonreceptor tyrosine kinase), clathrin, dynamin, SCAMPs (secretory carrier membrane proteins), lasp-1, actin, ezrin, coro-nin, myosin Vb, and myosin light chain kinases. For activity the pump needs to be associated with K+ and Cl3 conductive pathways. There is a huge H+ concentration gradient across the parietal cells (the lumen has 2-4 x 106 greater H+ concentration than the blood); consequently, the cells require a great deal of energy and, as a result, mitochondria make up 34% of cell volume. The processes of HCl secretion are shown in Figure 4.

The H+/K+ pump is a noncovalent dimer of an a (catalytic subunit) and a fi glycosylated subunit. The fi subunit targets the pump to the apical membrane and protects the catalytic subunit from degradation. Acid secretion requires both subunits. The a subunit (mol. wt 100000) consists of 10 membrane-spanning

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