Modulation of the ionic permeability of renal cortical brush-border membranes by cAMP

The effects of adenosine 3',5'-cyclic monophosphate (cAMP) on potassium chloride permeability, relative ionic permeabilities, and Na+-dependent glucose transport were examined in rat renal cortical membrane vesicles. Brush-border membrane vesicles were prepared from paired control and cAMP- or forskolin-exposed homogenates by use of a magnesium aggregation technique. These studies demonstrate that exposure to exogenous cAMP or increases in endogenous cAMP significantly increase KCl permeability and ionic chloride permeability relative to that of potassium (PCl/PK) as determined with the fluorescent potential-sensitive probe 3,3'-dipropylthiadicarbocyanine iodide [diS-C3-(5)] and 36Cl uptake. Because PNa/PK did not change, PCl/PNa was also significantly increased by cAMP. These changes in ionic permeabilities were associated with a significant stimulation of Na+-dependent glucose transport that was unassociated with either an alteration in the kinetics of glucose transport or delayed dissipation of the inwardly directed Na+ gradient. These findings indicate that the cAMP-induced stimulation of glucose transport resulted from hyperpolarization of the vesicles secondary to the increase in PCl/PNa. These studies suggest that in vivo variations in intracellular cAMP concentration may modulate electrogenic transport processes by altering relative ionic permeabilities and membrane potential in renal proximal tubule cells.