The isolated polycystin-1 cytoplasmic COOH terminus prolongs ATP-stimulated Cl- conductance through increased Ca2+ entry

Scott S. Wildman, Kimberly M. Hooper, Clare M. Turner, James S.K. Sham, Edward G. Lakatta, Brian F. King, Robert J. Unwin, Michael Sutters

Research output: Contribution to journalArticle


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 a link between polycystin-1 (the PKD1 gene product) and ATP-stimulated Cl - secretion in renal tubule cells. To do this, we performed a whole cell patch-clamp 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 ATP-stimulated Cl- conductance and intracellular Ca 2+ responses. Both effects were dependent on extracellular Ca 2+. It was determined that expression of the truncated polycystin-1 fusion protein introduced, or activated, an ATP-induced Ca2+ 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 Ca2+ homeostasis and indicate that dysregulated Ca2+ entry might promote Cl- secretion and cyst expansion in ADPKD.

Original languageEnglish (US)
Pages (from-to)F1168-F1178
JournalAmerican Journal of Physiology - Renal Physiology
Issue number6 54-6
StatePublished - Dec 2003


  • Autosomal dominant polycystic kidney disease
  • Chloride channels
  • Kidney collecting tubules
  • Patch-clamp techniques
  • Purinergic P receptors

ASJC Scopus subject areas

  • Physiology
  • Urology

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