This Article Full Text Full Text (PDF) All Versions of this Article: 2006-0003OCv1 35/2/243    most recent Alert me when this article is cited Alert me if a correction is posted Services 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 White, T. A. Articles by Wylam, M. E. Search for Related Content PubMed PubMed Citation Articles by White, T. A. Articles by Wylam, M. E.

Role of Transient Receptor Potential C3 in TNF-–Enhanced Calcium Influx in Human Airway Myocytes

Departments of Allergy and Immunology, Medicine, Anesthesiology, and Physiology and Biomedical Engineering, College of Medicine, Mayo Clinic, Rochester, Minnesota

Correspondence and requests for reprints should be addressed to Mark E. Wylam, M.D., Division of Pulmonary and Critical Care, College of Medicine, Mayo Clinic and Foundation, Rochester, MN 55905. E-mail: wylam.mark{at}mayo.edu

Previous studies have suggested that the proinflammatory cytokine, TNF-, contributes to airway hyperresponsivness by altering airway smooth muscle (ASM) Ca²⁺ responses to agonist stimulation. The present study examined the effects of TNF- on Ca²⁺ influx pathways in cultured human ASM cells (HASMCs). Proteins encoded by the transient receptor potential (TRP) gene family function as channels through which receptor-operated and store-operated Ca²⁺ entry (SOCE) occur. In the present study, the presence of TRPC1, TRPC3, TRPC4, TRPC5, and TRPC6 mRNA and protein expression was confirmed in cultured HASMCs using RT-PCR and Western blot analysis. TNF- treatment significantly increased TRPC3 mRNA and protein levels in HASMCs as well as SOCE. TNF- treatment also increased both the peak and plateau intracellular Ca²⁺ concentration responses in HASMCs elicited by acetylcholine and bradykinin. The effects of TNF- treatment on SOCE and agonist-induced intracellular Ca²⁺ concentration responses were attenuated using small interfering RNA transfection, which knocked down TRPC3 expression. Thus, in inflammatory airway diseases, TNF- treatment may result in increased myocyte activation due to altered Ca²⁺ influx pathways. These results suggest that TRPC3 may be an important therapeutic target in inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease.

Key Words: human airway smooth muscle • receptor-operated calcium entry • store-operated calcium entry • TNF- • transient receptor potential channels

This article has been cited by other articles:

				Y. S. Prakash, M. A. Thompson, and C. M. Pabelick Brain-Derived Neurotrophic Factor in TNF-{alpha} Modulation of Ca2+ in Human Airway Smooth Muscle Am. J. Respir. Cell Mol. Biol., November 1, 2009; 41(5): 603 - 611. [Abstract] [Full Text] [PDF]

				V. Sathish, M. A. Thompson, J. P. Bailey, C. M. Pabelick, Y. S. Prakash, and G. C. Sieck Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca2+ reuptake in human airway smooth muscle Am J Physiol Lung Cell Mol Physiol, July 1, 2009; 297(1): L26 - L34. [Abstract] [Full Text] [PDF]

				E. Y. Kim, C. P. Alvarez-Baron, and S. E. Dryer Canonical Transient Receptor Potential Channel (TRPC) 3 and TRPC6 Associate with Large-Conductance Ca2+-Activated K+ (BKCa) Channels: Role in BKCa Trafficking to the Surface of Cultured Podocytes Mol. Pharmacol., March 1, 2009; 75(3): 466 - 477. [Abstract] [Full Text] [PDF]

				J. Abramowitz and L. Birnbaumer Physiology and pathophysiology of canonical transient receptor potential channels FASEB J, February 1, 2009; 23(2): 297 - 328. [Abstract] [Full Text] [PDF]

				P. B. Helli and L. J. Janssen Properties of a store-operated nonselective cation channel in airway smooth muscle Eur. Respir. J., December 1, 2008; 32(6): 1529 - 1538. [Abstract] [Full Text] [PDF]

				D. L. Clarke, A. Sutcliffe, K. Deacon, D. Bradbury, L. Corbett, and A. J. Knox PKC{beta}II Augments NF-{kappa}B-Dependent Transcription at the CCL11 Promoter via p300/CBP-Associated Factor Recruitment and Histone H4 Acetylation J. Immunol., September 1, 2008; 181(5): 3503 - 3514. [Abstract] [Full Text] [PDF]

				D. Shan, R. B. Marchase, and J. C. Chatham Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes Am J Physiol Cell Physiol, March 1, 2008; 294(3): C833 - C841. [Abstract] [Full Text] [PDF]

				G. C. Sieck, T. A. White, M. A. Thompson, C. M. Pabelick, M. E. Wylam, and Y. S. Prakash Regulation of store-operated Ca2+ entry by CD38 in human airway smooth muscle Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L378 - L385. [Abstract] [Full Text] [PDF]

				J. A. Jude, M. E. Wylam, T. F. Walseth, and M. S. Kannan Calcium Signaling in Airway Smooth Muscle Proceedings of the ATS, January 1, 2008; 5(1): 15 - 22. [Abstract] [Full Text] [PDF]

				S. Hirota, P. Helli, and L. J. Janssen Ionic mechanisms and Ca2+ handling in airway smooth muscle Eur. Respir. J., July 1, 2007; 30(1): 114 - 133. [Abstract] [Full Text] [PDF]

				J. M. Dai, K.-H. Kuo, J. M. Leo, P. D. Pare, C. van Breemen, and C.-H. Lee Acetylcholine-Induced Asynchronous Calcium Waves in Intact Human Bronchial Muscle Bundle Am. J. Respir. Cell Mol. Biol., May 1, 2007; 36(5): 600 - 608. [Abstract] [Full Text] [PDF]

				Y. Amrani TNF-{alpha} and Calcium Signaling in Airway Smooth Muscle Cells: A Never-Ending Story with Promising Therapeutic Relevance Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 387 - 388. [Full Text] [PDF]