Mechanisms of H+ injury in rabbit esophageal epithelium.
We previously postulated that active Na transport by the esophageal stratified squamous epithelium is important for maintenance of its barrier function. To investigate this further we studied the effects of HCl on the in vivo esophageal potential difference (PD), on in vitro Na transport, and on esophageal Na-K-ATPase activity. In vivo esophageal perfusion with low concentrations of HCl (20 or 40 mM) increased the PD and a high concentration (120 mM) decreased it. An intermediate concentration (80 mM) caused a biphasic response with an initial increase in PD followed by a progressive decrease in PD. In vitro transport studies were performed to explain the increased in vivo PD. In the presence of luminal H+ the increased PD resulted from H+ diffusion from lumen to blood, whereas after H+ exposure the increased PD was due largely to increased net Na transport from lumen to blood through an amiloride-sensitive mechanism. In tissues with prolonged exposure to 80 mM HCl (PD decreased 80-100%), Na-K-ATPase activity was significantly inhibited (1.94 +/- 0.32 vs. 5.12 +/- 0.73 mumol P X mg prot-1 X h-1). Thus, HCl initially increases the in vivo esophageal PD by H+ transport from lumen to blood, a process replaced by stimulated net Na transport when H+ is replaced by Na. Prolonged acid exposure ultimately decreases Na exit from cells by inhibiting Na-K-ATPase activity. This sequence suggests that alterations in Na transport could result in cell edema and necrosis via loss of cell volume regulation.
D000818:Animals; D001692:Biological Transport; D001696:Biomechanical Phenomena; D002712:Chlorides / Q000378:metabolism; D004195:Disease Models, Animal; D004594:Electrophysiology; D004848:Epithelium / Q000503:physiopathology; D004947:Esophagus / Q000201:enzymology; D005764:Gastroesophageal Reflux / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D006863:Hydrogen-Ion Concentration; D008297:Male; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D002712:Chlorides; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase