Morphological factors influencing transepithelial permeability: a model for the resistance of the zonula occludens

Epithelial cells are joined at their apical surfaces by zonulae occludentes. Claude and Goodenough (1973) demonstrated a correlation between the structure of the zonula occludens as seen in freeze-fracture preparations and the passive electrical permeability of several simple epithelia. In epithelia with high transepithelial resistance, the zonula occludens consisted of many strands. In epithelia with low transepithelial resistance the zonula occludens was much reduced, sometimes consisting of only one strand. Evidence is reviewed here that indicates that in a number of simple epithelia the structure of the zonula occludens is largely responsible for the magnitude of transepithelial conductance. An equation is derived relating transepithelial junctional resistance to the number of junctional strands: R = RminP-N where R is the transepithelial resistance of the zonula occludens, Rmin is the minimum resistance of the junction (as when there are no strands in the zonula occludens), p is the probability a given strand is "open" and n is the number of strands in the junction. Using published experimental values of R and n for different epithelia, the calculated value of p was found to be as high as 0.4, which suggests that the strands in the zonula occludens are remarkably labile. Other morphological parameters relevant to transepithelial permeability are also considered, such as the width and depth of the intercelllar spaces, and the size of the epithelial cells themselves.