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 journalArticlepeer-review


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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