Paracellular back-diffusion of H+ across bullfrog fundic mucosa resulting from Ca2+ depletion and its effects on taurocholate-induced mucosal injury.

The effects of calcium depletion (by washout and by chelation with EDTA) on the net appearance of hydrogen ions (H+) on the secretory surface of in vitro sheets of bullfrog fundic mucosa have been studied. A CO2 distribution method was used to distinguish between true and apparent inhibition of H+ secretion. Our data indicate that Ca2+ depletion produces apparent inhibition of H+ secretion by increasing paracellular back-diffusion of H+ across the mucosa. Ca2+ washout resulted in a decrement of measurable H+ (1.42 +/- 0.07 to 0.93 +/- 0.09 muEq/cm2 hr-1, P less than 0.05) without altering delta CO2 (1.18 +/- 0.15 to 1.26 +/- 0.17 muEq/cm2 hr-1, not significant). Chelation of Ca2+ with EDTA produced a similar decrease in H+ (1.61 +/- 0.09 to 0.78 +/- 0.12 muEq/cm2 hr-1, P less than 0.05) without affecting delta CO2 (1.60 +/- 0.13 to 1.68 +/- 0.22 muEq/cm2 hr-1, not significant). The possibility that H+ back-diffusion (induced by Ca2+ depletion) via a paracellular shunt might ameliorate injury was examined in bullfrog fundic mucosa exposed to a bile salt. H+ secretion, potential difference, resistance, and ultrastructural changes were studied in isolated mucosal sheets treated with 10 mM sodium taurocholate with or without Ca2+ depletion. Measurable H+, potential difference, and resistance were significantly lower in the Ca2+ depleted tissues. Scanning electron microscopy revealed identical changes in the surface epithelial cells of both depleted and nondepleted mucosae, but there was significantly less cell loss from depleted mucosae (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)