IMMUNOLOCALIZATION OF ION-TRANSPORT PROTEINS IN HUMAN AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY EPITHELIAL-CELLS

The kidneys of patients with autosomal dominant polycystic kidney dise ase become massively enlarged due to the progressive expansion of myri ad fluid-filled cysts. The epithelial cells that line the cyst walls a re responsible for secreting the cyst fluid, but the mechanism through which this secretion occurs is not well established. Recent studies s uggest that renal cyst epithelial cells actively secrete Cl across the ir apical membranes, which in turn drives the transepithelial movement of Na and water. The characteristics of this secretory flux suggest t hat it is dependent upon the participation of an apical cystic fibrosi s transmembrane conductance regulator (CFTR)-like Cl channel and basol ateral Na,K-ATPase. To test this hypothesis, we have immunolocalized t he CFTR and Na,K-ATPase proteins in intact cysts and in cyst epithelia l cells cultured in vitro on permeable filter supports. In both settin gs, cyst epithelial cells were found to possess Na,K-ATPase exclusivel y at their basolateral surfaces; apical labeling was not detected. The CFTR protein was present at the apical surfaces of cyst epithelial ce lls that had been stimulated to secrete through incubation in forskoli n. CFTR was detected in intracellular structures in cultured cyst epit helial cells that had not received the forskolin treatment. These resu lts demonstrate that the renal epithelial cells that line cysts in aut osomal dominant polycystic kidney disease express transport systems wi th the appropriate polarity to mediate active Cl and fluid secretion.