Network thermodynamic modeling of hormone regulation of active Na+ transport in cultured renal epithelium (A6).

A network thermodynamic model was developed to describe steady-state ion flows (Na+,K+, and Cl-) and related electrical events in a cultured renal epithelium (A6) derived from toad kidney. Three hypotheses for explaining the steady-state increases in short-circuit current (SCC) produced by aldosterone and/or insulin were examined using the model. Changing only the number of basolateral Na+-K+ pumps produced virtually no change in SCC and was ruled out. Changing only the number of apical Na+ channels could produce sufficient increases in SCC but presented problems in the pattern of changes produced in cell ion concentrations and therefore appeared unlikely. Changing both apical and basolateral parameters in a balanced, coordinated manner produced the maximal changes in SCC with the minimal changes in cell ion concentrations and appeared to be the "best" hypothesis. In addition, it was found necessary for tight junction permeability to increase as active Na+ transport increased under open-circuit conditions. Simulations, using these results, compared favorably with experimental data on the stimulatory effects of aldosterone and insulin, both separately and together, on active Na+ transport.