Skip to main content

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

Wildman, Scott S.P., Hooper, Kimberly M., Turner, Clare M., Sham, James S. K., Lakatta, Edward G., King, Brian F., Unwin, Robert J., Sutters, Michael (2003) The isolated polycystin-1 cytoplasmic COOH terminus prolongs ATP-stimulated Cl- conductance through increased Ca2+ entry. American Journal of Physiology. Renal physiology, 285 (6). F1168-F1178. ISSN 1931-857X. E-ISSN 1522-1466. (doi:10.1152/ajprenal.00171.2003) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:52968)

PDF Publisher pdf
Language: English

Restricted to Repository staff only
Contact us about this Publication
[thumbnail of F1168.full.pdf]
Official URL


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 Ca2+ responses. Both effects were dependent on extracellular Ca2+. 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.

Item Type: Article
DOI/Identification number: 10.1152/ajprenal.00171.2003
Uncontrolled keywords: autosomal dominant polycystic kidney disease; purinergic P2 receptors; chloride channels; kidney collecting tubules; patch-clamp techniques
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Scott S.P. Wildman
Date Deposited: 09 Dec 2015 17:23 UTC
Last Modified: 16 Feb 2021 13:31 UTC
Resource URI: (The current URI for this page, for reference purposes)
  • Depositors only (login required):


Downloads per month over past year