Influence of lateral intercellular spaces on current propagation in tubular epithelia as estimated by a multi-cable model

Abstract

A multiple cable model has been developed for tubular epithelia which allows current flow along the tubular lumen, along the cell layer and inside the lateral intercellular space (LIS) to be quantitatively assessed. In this model tubular lumen and cell layer are represented by two concentric cylinders and the LIS by n concentric interconnected fluid layers which are interposed between the cells, contact the lateral cell membranes and extend all along the tubular length. The innermost LIS layer connects to the tight junctions and the outermost layer to the peritubular space. Modelling each element by a cable-like structure the mathematical solution leads to n + 2 linear combinations of n + 2 exponential functions. Based on morphometric data and resistance measurements on Necturus proximal tubule [4,10] model calculations have been performed of the voltage attenuation along tubular lumen, cell layer and LIS for n = 3 or n = 6 assuming different LIS widths (0.02, 0.2, and 2.0 micron). The results show that the influence of LIS is insignificant in Necturus proximal tubule under control conditions, but may become significant in other functional states or other tubules. Collapsing the LIS increases predominantly the shunt resistance and the effective resistance of the lateral cell membrane but longitudinal current propagation along the LIS remains negligible at all space widths. In addition, model calculations are presented which allow errors in determining tight junction resistance and cell membrane resistances from a simple cable model to be quantified as function of LIS width.