Contribution of junctional conductance to the cellular voltage-divider ratio in frog skins

It has been suggested that distribution of lateral interspace resistance in association with a highly conductive junction can significantly affect the measurement of outer membrane(o)/epithelial(t) voltage divider ratios (Fo = delta Vo/delta Vt), thereby leading to erroneous inferences regarding the outer membrane fractional resistance [fRo = Ro/Rc = Ro/(Ro + Ri)], where Ro and Ri are the outer and inner cell membrane resistance respectively and Rc is the total cell membrane resistance. We present here experimental evidence for this point of view. During seasons when frog skins were highly permeable to Cl, transepithelial conductance gt often exceeded 2 mS/cm2. High concentrations of external amiloride rapidly blocked cellular transport, but gt initially remained high and Fo remained appreciably less than 1.0. These values of Fo were found here to result from low junctional resistance Rj: increase of Rj, either gradually following the administration of amiloride, or abruptly with external replacement of Cl by other anions, was associated with increase of Fo to near unity, without effect on the membrane potential or significant change in the short-circuit current. Experimental results following amiloride validated a simple equivalent circuit model predicting near-linear increase in Fo with progressive decrease in gt and led to plausible values of Rj and lateral space resistance Rl. The possible influence of the paracellular resistance pattern on the evaluation of cell membrane resistances from voltage divider ratios is discussed.