title: Computer modeling of gastric parietal cell: significance of canalicular space, gland lumen, and variable canalicular [K+].
abstract: A computer model, constructed for evaluation of integrated functioning of cellular components involved in acid secretion by the gastric parietal cell, has provided new interpretations of older experimental evidence, showing the functional significance of a canalicular space separated from a mucosal bath by a gland lumen and also shedding light on basolateral Cl(-) transport. The model shows 1) changes in levels of parietal cell secretion (with stimulation or H-K-ATPase inhibitors) result mainly from changes in electrochemical driving forces for apical K(+) and Cl(-) efflux, as canalicular [K(+)] ([K(+)]can) increases or decreases with changes in apical H(+)/K(+) exchange rate; 2) H-K-ATPase inhibition in frog gastric mucosa would increase [K(+)]can similarly with low or high mucosal [K(+)], depolarizing apical membrane voltage similarly, so electrogenic H(+) pumping is not indicated by inhibition causing similar increase in transepithelial potential difference (Vt) with 4 and 80 mM mucosal K(+); 3) decreased H(+) secretion during strongly mucosal-positive voltage clamping is consistent with an electroneutral H-K-ATPase being inhibited by greatly decreased [K(+)]can (Michaelis-Menten mechanism); 4) slow initial change ("long time-constant transient") in current or Vt with clamping of Vt or current involves slow change in [K(+)]can; 5) the Na(+)-K(+)-2Cl(-) symporter (NKCC) is likely to have a significant role in Cl(-) influx, despite evidence that it is not necessary for acid secretion; and 6) relative contributions of Cl(-)/HCO3 (-) exchanger (AE2) and NKCC to Cl(-) influx would differ greatly between resting and stimulated states, possibly explaining reported differences in physiological characteristics of stimulated open-circuit Cl(-) secretion (≈H(+)) and resting short-circuit Cl(-) secretion (>>H(+)).
authors: Department of Molecular and Cell Biology, University of California, Berkeley, California crothers@berkeley.edu.
authors: James M
authors: 0000-0003-2918-3587
authors: JM
authors: Crothers
authors: Department of Molecular and Cell Biology, University of California, Berkeley, California.
authors: John G
authors: JG
authors: Forte
authors: Department of Molecular and Cell Biology, University of California, Berkeley, California.
authors: Terry E
authors: TE
authors: Machen
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D003198:Computer Simulation; D006801:Humans; D016623:Ion Pumps / Q000378:metabolism; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D002712:Chlorides; D016623:Ion Pumps; D011188:Potassium
keywords: H-K-ATPase; long time constant; proton-pump inhibitor; short circuit; voltage clamp