The structures that contribute to shunt resistance (Rs) in esophageal epithelium are incompletely understood, with 35–40% of Rs known to be calcium-dependent, reflecting the role of e-cadherin. Two calcium-independent candidates for the remaining ~60% of Rs have been identified: the glycoprotein matrix (GPM) within stratum corneum of esophageal epithelium, and the lateral cell membranes (LCMs) from neighboring cells. To determine the contribution of GPM and LCMs to Rs, rabbit esophageal epithelium was mounted in Ussing chambers so that transepithelial resistance (RT), a marker of Rs, could be monitored during luminal exposure to either glycosidases for disruption of the GPM or to hypertonic urea for separation of the LCMs. Glycosidases had no effect on RT. In contrast, hypertonic urea reduced RT, increased fluorescein flux and widened the intercellular spaces. That urea reduced RT, and so Rs, by widening the intercellular spaces, and not by altering the e-cadherin-dependent apical junctional complex, was supported by the ability of: (a) calcium-free solution to reduce RT beyond that produced by urea, (b) hypertonic urea to reduce RT beyond that produced by calcium free solution, (c) hypertonic sucrose to collapse the intercellular spaces and raise RT, and (d) empigen, a zwitterionic detergent, to non-osmotically widen the intercellular spaces and reduce RT. These data indicate that the LCMs from neighboring cells are a major contributor to shunt resistance in esophageal epithelium. As resistor, they are distinguishable from the apical junctional complex by their sensitivity to (luminal) hypertonicity and insensitivity to removal of calcium.
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