Aldosterone interaction on sodium transport and chloride permeability: influence of epithelial structure.

The effects of aldosterone on sodium transport and chloride permeability were investigated by electrophysiology in two structurally distinct epithelial used as models for the distal renal tubule: the A6 cell monolayer as compared with the amphibian skin epithelium (ASE). Short-circuit current (Isc) and transepithelial conductance (Gt) were measured in A6 monolayers incubated overnight with(out) aldosterone. Cell and shunt conductances (Gcell and Gsh) were also determined, as well as the conductive nature of the chloride pathway. These parameters were correlated with sodium and chloride fluxes in A6 cells (JNa and JCl) and compared with the data recorded across ASE (Bufo marinus). The existence of a cAMP-dependent chloride secretory pathway in A6 cells was also investigated upon exposition to arginine vasopressin (AVP) or oxytocin. When A6 monolayers were incubated with aldosterone, Gt significantly increased with respect to control preparations; this increase resulted solely from an increase in Gcell, and was reflected by a 3-fold increase in Isc. There was a significant relationship between Isc and Gcell, as well as between Isc and JNa in both control and aldosterone-stimulated preparations. The A6 clone used was devoid of cAMP-dependent chloride secretory activity and was unresponsive to AVP or oxytocin. Thus, comparison between ASE and A6 preparations revealed two major differences: unlike ASE, (i) aldosterone has no effect on Gsh and (ii) no conductive reabsorptive chloride pathway is operative in A6 monolayers tested. In addition, cobalt had no effect on electrical parameters of A6 monolayers. These observations show that difference in epithelial structure is reflected in terms of electrophysiological response to aldosterone, which suggests that cell heterogeneity could be a prerequisite for observing a conductive reabsorptive chloride pathway in aldosterone-responsive, sodium-transporting epithelia