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Published ahead of print on July 18, 2003, doi:10.1165/rcmb.2003-0134OC

Am. J. Respir. Cell Mol. Biol., Volume 30, Number 2, February 2004, 145-154

A more recent version of this article appeared on February 1, 2004
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Submitted on April 11, 2003
Revised on July 15, 2003

EXPRESSION OF TRPC6 AND RELATED TRP FAMILY MEMBERS IN HUMAN AIRWAY SMOOTH MUSCLE AND LUNG TISSUE

Randolph L Corteling1, Su Li2, June Giddings2, John Westwick2, Chris Poll2, and Ian P Hall1*

1 Division of Therapeutics and Molecular Medicine, University of Nottingham, Nottingham, Nottingham, United Kingdom, 2 Novartis Respiratory Research Centre, Novartis Pharmaceuticals, Horsham, West Sussex, United Kingdom

* To whom correspondence should be addressed. E-mail: ian.hall{at}nottingham.ac.uk.

Elevation of the intracellular free Ca2+ concentration ([Ca2+]i) regulates many functional responses in airway smooth muscle, including contraction, proliferation, adhesion and cell survival. This increase in calcium can be achieved by a release from internal stores (sarcoplasmic reticulum) and/or entry across the cell membrane from the extracellular environment. The molecular identity of this calcium influx pathway in human airway smooth muscle (HASM) remains unclear. Functional studies using Fluo 4-loaded HASM suggest the presence of a histamine H1 receptor-activated Ca2+ entry pathway with characteristics similar to those seen with TRP (transient receptor potential) family homologues. Using a range of molecular and cell biological approaches we defined the expression pattern of TRPC homologues in airway cells and tissue. Here we show that HASM and human bronchial epithelial cells (HBEC) both express TRPC 1, 4, and 6, with HASM also expressing TRPC3 at the mRNA level. Identification of TRPC6 protein by western blot and confocal microscopy indicated that the protein is localized in specific cell types, suggesting it plays an important role in regulating key functions in airway cells. These data demonstrate the expression of a range of TRPC homologues in the airway and the presence of a functional Ca2+ entry pathway with characteristics typical of TRPC family members. TRPC homologues may provide an important novel target for the treatment of airway disease.




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