HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: fj.08-119495v1 23/2/297    most recent Alert me when this article is cited Alert me if a correction is posted 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 Abramowitz, J. Articles by Birnbaumer, L. Search for Related Content PubMed PubMed Citation Articles by Abramowitz, J. Articles by Birnbaumer, L.

Physiology and pathophysiology of canonical transient receptor potential channels

Transmembrane Signaling Group, Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA

¹ Correspondence: Transmembrane Signaling Group, Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA. E-mail: J.A., abramow1{at}niehs.nih.gov; L.B., birnbau1{at}niehs.nih.gov

The existence of a mammalian family of TRPC ion channels, direct homologues of TRP, the visual transduction channel of flies, was discovered during 1995–1996 as a consequence of research into the mechanism by which the stimulation of the receptor-Gq-phospholipase Cβ signaling pathway leads to sustained increases in intracellular calcium. Mammalian TRPs, TRPCs, turned out to be nonselective, calcium-permeable cation channels, which cause both a collapse of the cell’s membrane potential and entry of calcium. The family comprises 7 members and is widely expressed. Many cells and tissues express between 3 and 4 of the 7 TRPCs. Despite their recent discovery, a wealth of information has accumulated, showing that TRPCs have widespread roles in almost all cells studied, including cells from excitable and nonexcitable tissues, such as the nervous and cardiovascular systems, the kidney and the liver, and cells from endothelia, epithelia, and the bone marrow compartment. Disruption of TRPC function is at the root of some familial diseases. More often, TRPCs are contributing risk factors in complex diseases. The present article reviews what has been uncovered about physiological roles of mammalian TRPC channels since the time of their discovery. This analysis reveals TRPCs as major and unsuspected gates of Ca²⁺ entry that contribute, depending on context, to activation of transcription factors, apoptosis, vascular contractility, platelet activation, and cardiac hypertrophy, as well as to normal and abnormal cell proliferation. TRPCs emerge as targets for a thus far nonexistent field of pharmacological intervention that may ameliorate complex diseases.—Abramowitz, J., Birnbaumer, L. Physiology and pathophysiology of canonical transient receptor potential channels.

Key Words: calcium • cardiovascular system • epithelium • lung • neuron

This article has been cited by other articles:

				M. Ju, J. Shi, S. N. Saleh, A. P. Albert, and W. A. Large Ins(1,4,5)P3 interacts with PIP2 to regulate activation of TRPC6/C7 channels by diacylglycerol in native vascular myocytes J. Physiol., May 1, 2010; 588(9): 1419 - 1433. [Abstract] [Full Text] [PDF]

				X. Wu, P. Eder, B. Chang, and J. D. Molkentin TRPC channels are necessary mediators of pathologic cardiac hypertrophy PNAS, April 13, 2010; 107(15): 7000 - 7005. [Abstract] [Full Text] [PDF]

				N. Zanou, G. Shapovalov, M. Louis, N. Tajeddine, C. Gallo, M. Van Schoor, I. Anguish, M. L. Cao, O. Schakman, A. Dietrich, et al. Role of TRPC1 channel in skeletal muscle function Am J Physiol Cell Physiol, January 1, 2010; 298(1): C149 - C162. [Abstract] [Full Text] [PDF]

				K. Miyagi, S. Kiyonaka, K. Yamada, T. Miki, E. Mori, K. Kato, T. Numata, Y. Sawaguchi, T. Numaga, T. Kimura, et al. A Pathogenic C Terminus-truncated Polycystin-2 Mutant Enhances Receptor-activated Ca2+ Entry via Association with TRPC3 and TRPC7 J. Biol. Chem., December 4, 2009; 284(49): 34400 - 34412. [Abstract] [Full Text] [PDF]

				S. A. Gross, G. A. Guzman, U. Wissenbach, S. E. Philipp, M. X. Zhu, D. Bruns, and A. Cavalie TRPC5 Is a Ca2+-activated Channel Functionally Coupled to Ca2+-selective Ion Channels J. Biol. Chem., December 4, 2009; 284(49): 34423 - 34432. [Abstract] [Full Text] [PDF]

				B. Pani, H. L. Ong, S.-c. W. Brazer, X. Liu, K. Rauser, B. B. Singh, and I. S. Ambudkar Activation of TRPC1 by STIM1 in ER-PM microdomains involves release of the channel from its scaffold caveolin-1 PNAS, November 24, 2009; 106(47): 20087 - 20092. [Abstract] [Full Text] [PDF]

				S. Costello, F. Michelangeli, K. Nash, L. Lefievre, J. Morris, G. Machado-Oliveira, C. Barratt, J. Kirkman-Brown, and S. Publicover Ca2+-stores in sperm: their identities and functions Reproduction, September 1, 2009; 138(3): 425 - 437. [Abstract] [Full Text] [PDF]

				S. Kiyonaka, K. Kato, M. Nishida, K. Mio, T. Numaga, Y. Sawaguchi, T. Yoshida, M. Wakamori, E. Mori, T. Numata, et al. Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound PNAS, March 31, 2009; 106(13): 5400 - 5405. [Abstract] [Full Text] [PDF]