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This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/F978    most recent 00260.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (22) Citing Articles via Google Scholar Google Scholar Articles by Liu, W. Articles by Satlin, L. M. Search for Related Content PubMed PubMed Citation Articles by Liu, W. Articles by Satlin, L. M.

Mechanoregulation of intracellular Ca²⁺ concentration is attenuated in collecting duct of monocilium-impaired orpk mice

¹Department of Pediatrics, Mount Sinai School of Medicine, New York, New York; ²Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio; ³Department of Biomedical Engineering, The City College of New York and City University of New York Graduate School, New York, New York; and ⁴Department of Cell Biology and ⁵Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama

Submitted 14 July 2004 ; accepted in final form 9 June 2005

Autosomal recessive polycystic kidney disease (ARPKD) is characterized by the progressive dilatation of collecting ducts, the nephron segments responsible for the final renal regulation of sodium, potassium, acid-base, and water balance. Murine models of ARPKD possess mutations in genes encoding cilia-associated proteins, including Tg737 in orpk mice. New findings implicate defects in structure/function of primary cilia as central to the development of polycystic kidney disease. Our group (Liu W, Xu S, Woda C, Kim P, Weinbaum S, and Satlin LM, Am J Physiol Renal Physiol 285: F998–F1012, 2003) recently reported that increases in luminal flow rate in rabbit collecting ducts increase intracellular Ca²⁺ concentration ([Ca²⁺]_i) in cells therein. We thus hypothesized that fluid shear acting on the apical membrane or hydrodynamic bending moments acting on the cilium increase renal epithelial [Ca²⁺]_i. To further explore this, we tested whether flow-induced [Ca²⁺]_i transients in collecting ducts from mutant orpk mice, which possess structurally abnormal cilia, differ from those in controls. Isolated segments from 1- and 2-wk-old mice were microperfused in vitro and loaded with fura 2; [Ca²⁺]_i was measured by digital ratio fluorometry before and after the rate of luminal flow was increased. All collecting ducts responded to an increase in flow with an increase in [Ca²⁺]_i, a response that appeared to be dependent on luminal Ca²⁺ entry. However, the magnitude of the increase in [Ca²⁺]_i in 2- but not 1-wk-old mutant orpk animals was blunted. We speculate that this defect in mechano-induced Ca²⁺ signaling in orpk mice leads to aberrant structure and function of the collecting duct in ARPKD.

autosomal recessive polycystic kidney disease; calcium signaling; principal cell; intercalated cell; differentiation

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