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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)

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Abstract

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: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Scott S.P. Wildman
Date Deposited: 09 Dec 2015 17:23 UTC
Last Modified: 29 May 2019 16:40 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/52968 (The current URI for this page, for reference purposes)
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