Nonhormonal mechanisms for the regulation of transepithelial sodium transport: The roles of surface potential and cell calcium

An attempt to define the main categories of regulatory mechanisms of transepithelial sodium transport across tight epithelia is presented. In particular, evidence suggesting two types of mechanisms, changes in surface potential and the level of cell Ca, are described in greater detail. We have measured the effects of conditions that affect surface potential on the transepithelial sodium transport. Those conditions that increase the screening of negative charge and therefore depolarize the outer membrane are expected to have effects homologous to a depolarization caused by external current. Indeed, when the composition of the outside solution was modified by (i) increasing ionic strength, (ii) adding polyvalent cations (La⁺⁺⁺, Co⁺⁺, Ni⁺⁺, Cd⁺⁺), or (iii) lowering pH, an increase in active Na transport was detected. Moreover, the presence of small concentrations of polyvalent cations which screen surface charge, markedly dampens or even eliminates the effects of pH or ionic strength on Na transport. These findings provide additional support for the notion that a potential-sensitive component regulates Na movements across the apical membrane of the frog skin, and offer a framework to understand the effects of numerous cationic agents on transepithelial transport that hitherto remain unexplained. With respect to the role of intracellular Ca we have found that procedures that increase cell Ca, like removal of sodium in the basal solution or addition of ionophore A23187, reduce transepithelial Na transport. Moreover, conditions that block the increase in cell Ca prevent the inhibition of transport. These observations suggest that the level of intracellular Ca may determine the rate of transepithelial Na transport.