The isolated polycystin-1 cytoplasmic COOH terminus prolongs ATP-stimulated Cl Ϫ conductance through increased Ca 2ϩ entry. The precise steps leading from mutation of the polycystic kidney disease (PKD1) gene to the autosomal dominant polycystic kidney disease (ADPKD) phenotype remain to be established. Fluid accumulation is a requirement for cyst expansion in ADPKD, suggesting that abnormal fluid secretion into the cyst lumen might play a role in disease. In this study, we sought to establish

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... link between polycystin-1 (the PKD1 gene product) and ATP-stimulated Cl Ϫ secretion in renal tubule cells. To do this, we performed a whole cell patchclamp analysis of the effects of expression of the isolated cytoplasmic COOH-terminus of polycystin-1 in stably transfected mouse cortical collecting duct cells. The truncated polycystin-1 fusion protein prolonged the duration of ATPstimulated Cl Ϫ conductance and intracellular Ca 2ϩ responses. Both effects were dependent on extracellular Ca 2ϩ . It was determined that expression of the truncated polycystin-1 fusion protein introduced, or activated, an ATP-induced Ca 2ϩ entry pathway that was undetectable in transfection control cell lines. Our findings are concordant with increasing evidence for a role of polycystin-1 in cell Ca 2ϩ homeostasis and indicate that dysregulated Ca 2ϩ entry might promote Cl Ϫ secretion and cyst expansion in ADPKD. autosomal dominant polycystic kidney disease; purinergic P 2