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This Article Full Text Full Text (PDF) All Versions of this Article: 566/2/309    most recent jphysiol.2005.087072v1 Services Email this article to a friend Similar articles in this journal 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 Google Scholar Google Scholar Articles by Montalbetti, N. Articles by Cantiello, H. F Search for Related Content PubMed PubMed Citation Articles by Montalbetti, N. Articles by Cantiello, H. F

¹ Laboratorio de Canales Iónicos, Departamento de Fisicoquímica y Química Analítica, Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina
² Department of Physiology, University of Alberta, Edmonton, Canada
³ Renal Unit, Department of Medicine, Massachusetts General Hospital and, Harvard Medical School, Charlestown, MA 02129, USA

The human syncytiotrophoblast (hST) is the most apical epithelial barrier that covers the villous tree of the human placenta. An intricate and highly organized network of cytoskeletal structures supports the hST. Recently, polycystin-2 (PC2), a TRP-type nonselective cation channel, was functionally observed in hST, where it may be an important player to Ca²⁺ transport. Little is known, however, about channel regulation in hST. In this report, the regulatory role of actin dynamics on PC2 channels reconstituted from hST apical membranes was explored. Acute addition of cytochalasin D (CD, 5 µg ml^–1) to reconstituted hST apical membranes transiently increased K⁺-permeable channel activity. The actin-binding proteins -actinin and gelsolin, as well as PC2, were observed by Western blot and immunofluorescence analyses in hST vesicles. CD treatment of hST vesicles resulted in a re-distribution of actin filaments, in agreement with the effect of CD on K⁺ channel activity. In contrast, addition of exogenous monomeric actin, but not prepolymerized actin, induced a rapid inhibition of channel function in hST. This inhibition was obliterated by the presence of CD in the medium. The acute (<15 min) CD stimulation of K⁺ channel activity was mimicked by addition of the actin-severing protein gelsolin in the presence, but not in the absence, of micromolar Ca²⁺. Ca²⁺ transport through PC2 triggers a regulatory feedback mechanism, which is based on the severing and re-formation of filamentous actin near the channels. Cytoskeletal structures may thus be relevant to ion transport regulation in the human placenta.

(Received 21 March 2005; accepted after revision 19 April 2005; first published online 21 April 2005)
Corresponding author H. F. Cantiello: Renal Unit, Massachusetts General Hospital East, Building 149, 13th Street, Charlestown, MA 02129, USA. Email: cantiello{at}helix.mgh.harvard.edu

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				N. Montalbetti, Q. Li, Y. Wu, X.-Z. Chen, and H. F. Cantiello Polycystin-2 cation channel function in the human syncytiotrophoblast is regulated by microtubular structures J. Physiol., March 15, 2007; 579(3): 717 - 728. [Abstract] [Full Text] [PDF]

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