Trans/paracellular, surface/crypt, and epithelial/subepithelial resistances of mammalian colonic epithelia

The epithelial barrier function of the large intestine resides in the trans - and paracellular pathways of the surface epithelium and crypts. Conventio nal transmural resistance and permeability measurements, however, yield onl y the resistance of the whole tissue and not that of its individual compone nts. Combining conductance scanning techniques and impedance analysis, we d etermined the resistance of epithelial and subepithelial tissues, crypts an d surface epithelium, and trans- and paracellular pathways of the mouse dis tal colon. The subepithelial tissue contributed 15% to the transmural resis tance of 118+/-9 Omega.cm(2). In the epithelium proper the resistance of cr ypts (429+/-86 Omega.cm(2)) exceeded that of the surface epithelium (132+/- 15 Omega.cm(2)). The paracellular resistance (3.2+/-0.4 k Omega.cm(2)) of t he surface epithelium was 23-fold. higher than the transcellular resistance (137+/-16 Omega.cm(2)), and thus the epithelium was classified as "medium tight". In order to investigate the trans- and paracellular resistances of the crypt epithelium as well, flat monolayers of HT-29/B6 cultured colon cr ypt cells were studied, which had a transepithelial resistance of 349+/-32 Omega.cm(2). With transcellular resistance (377+/-41 Omega.cm(2)) tenfold l ower than the paracellular resistance (3.9+/-1.3 Omega.cm(2)), this cryptal monolayer was also classified as "medium tight". Hence, considering the 1. 2 times larger area of the crypt epithelium, the surface epithelium has a 4 times larger ion permeability than the crypt epithelium. However, the para cellular resistances are not different. Thus the lower transcellular resist ance of the surface compared to the crypt epithelium suggests a higher dens ity of ion channels in the apical membrane of surface cells.