Dilated intercellular spaces: a morphological feature of acid reflux--damaged human esophageal epithelium.

BACKGROUND & AIMS: Dilated intercellular spaces are a sign of epithelial damage in acid-perfused rabbit esophagus, a change best identified by transmission electron microscopy. The aim of this study was to determine if this change is also a feature of acid damage to human esophageal epithelium. METHODS: Endoscopic esophageal biopsy specimens from patients with (n = 11) and without (n = 13) recurrent heartburn were examined using transmission electron microscopy. Of 11 patients with heartburn, 6 had erosive esophagitis and 5 had normal-appearing mucosa on endoscopy; 13 controls had no symptoms or signs of esophageal disease. Using a computer, intercellular space diameter was measured from transmission electron microscopy photomicrographs of the specimen from each patient. RESULTS: Intercellular space diameter was significantly greater in specimens from patients with heartburn than those from controls; this was true irrespective of whether the patient had erosive or nonerosive disease. Space diameters of > or = 2.4 microns were present in 8 of 11 patients with heartburn and in no controls. CONCLUSIONS: Dilated intercellular spaces are a feature of reflux damage to human esophageal epithelium. As a morphological marker of increased paracellular permeability, its presence in patients without endoscopic abnormalities may help explain their development of heartburn.

Potassium conductance in rabbit esophageal epithelium.

K+ conductance in apical and basolateral cell membranes of rabbit esophageal epithelial cells was investigated within intact epithelium by impalement with conventional microelectrodes from luminal or serosal sides. Under steady-state conditions, K+ conductance was demonstrated in basolateral, but not apical, membranes by showing 1) membrane depolarization upon exposure to either solutions high in K+ (20-65 mM) or containing Ba2+, tetraethylammonium, or quinine, and 2) a resistance ratio that increased on exposure to high K+ solution and decreased on exposure to Ba2+, quinine, and tetraethylammonium. From exposures to high K+, the apparent K+ transference number and electromotive force generated at the basolateral membrane were calculated and found to be 0.42 +/- 0.01 and -83 +/- 3 mV, respectively. Furthermore, basolateral K+ conductance was shown to be important for maintaining resting net transepithelial Na+ absorption in that high K+ or barium inhibited the transepithelial potential difference and short-circuit current of Ussing-chambered epithelia. We conclude that under steady-state conditions the basolateral, but not apical, membranes of esophageal epithelial cells contain a K(+)-conductive pathway and that this pathway is important for active sodium absorption.