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

J. Biol. Chem., Vol. 279, Issue 19, 19566-19573, May 7, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/19/19566    most recent M401481200v1 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 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 Stokes, L. Articles by Grafton, G. Search for Related Content PubMed PubMed Citation Articles by Stokes, L. Articles by Grafton, G. Social Bookmarking                      What's this?

Non-voltage-gated L-type Ca²⁺ Channels in Human T Cells

PHARMACOLOGY AND MOLECULAR CHARACTERIZATION OF THE MAJOR PORE-FORMING AND AUXILIARY -SUBUNITS^*

Leanne Stokes, John Gordon, and Gillian Grafton¶

From the Medical Research Council Centre for Immune Regulation, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom

In T lymphocytes, engagement of the antigen receptor leads to a biphasic Ca²⁺ flux consisting of a mobilization of Ca²⁺ from intracellular stores followed by a lower but sustained elevation that is dependent on extracellular Ca²⁺. The prolonged Ca²⁺ flux is required for activation of transcription factors and for subsequent activation of the T cell. Ca²⁺ influx requires as yet unidentified Ca²⁺ channels, which potentially play a role in T cell activation. Here we present evidence that human T cells express a non-voltage-gated Ca²⁺ channel related to L-type voltage-gated Ca²⁺ channels. Drugs that block classical L-type channels inhibited the initial phase of the antigen receptor-induced Ca²⁺ flux and could also inhibit the sustained phase of the Ca²⁺ signal suggesting a role for the L-type Ca²⁺ channel in antigen receptor signaling. T cells expressed transcripts for the ₁ 1.2 and ₁ 1.3 pore-forming subunits of L-type voltage-gated Ca²⁺ channels and transcripts for all four known -subunits including several potential new splice variants. Jurkat T leukemia cells expressed a small amount of full-length ₁1.2 protein but the dominant form was a truncated protein identical in size to a truncated ₁ 1.2 protein known to be expressed in B lymphocytes. They further expressed a truncated form of the ₁ 1.3 subunit and auxiliary 1- and 3-subunit proteins. Our data strongly suggest that functional but non-voltage-gated L-type Ca²⁺ channels are expressed at the plasma membrane in T cells and play a role in the antigen receptor-mediated Ca²⁺ flux in these cells.

Received for publication, February 10, 2004 , and in revised form, February 22, 2004.

^* This work was supported by the Medical Research Council (MRC) and the University of Birmingham School of Medicine. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Institute of Molecular Physiology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.

An MRC non-clinical research professor.

^¶ To whom correspondence should be addressed: MRC Centre for Immune Regulation, Institute of Biomedical Research, Medical School, University of Birmingham, Birmingham B15 2TT, UK. Tel.: 44-121-415-8687; Fax: 44-121-414-3599; E-mail: g.grafton{at}bham.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Badou, M. K. Jha, D. Matza, W. Z. Mehal, M. Freichel, V. Flockerzi, and R. A. Flavell Critical role for the beta regulatory subunits of Cav channels in T lymphocyte function PNAS, October 17, 2006; 103(42): 15529 - 15534. [Abstract] [Full Text] [PDF]

				M. Prakriya and R. S. Lewis Regulation of CRAC Channel Activity by Recruitment of Silent Channels to a High Open-probability Gating Mode J. Gen. Physiol., August 28, 2006; 128(3): 373 - 386. [Abstract] [Full Text] [PDF]

				B. Gomes, M. Savignac, M. D. Cabral, P. Paulet, M. Moreau, C. Leclerc, R. Feil, F. Hofmann, J.-C. Guery, G. Dietrich, et al. The cGMP/Protein Kinase G Pathway Contributes to Dihydropyridine-sensitive Calcium Response and Cytokine Production in TH2 Lymphocytes J. Biol. Chem., May 5, 2006; 281(18): 12421 - 12427. [Abstract] [Full Text] [PDF]

				J. R Robbins, S. M. Lee, A. H Filipovich, P. Szigligeti, L. Neumeier, M. Petrovic, and L. Conforti Hypoxia modulates early events in T cell receptor-mediated activation in human T lymphocytes via Kv1.3 channels J. Physiol., April 1, 2005; 564(1): 131 - 143. [Abstract] [Full Text] [PDF]

				D. J. Beech, K. Muraki, and R. Flemming Non-selective cationic channels of smooth muscle and the mammalian homologues of Drosophila TRP J. Physiol., September 15, 2004; 559(3): 685 - 706. [Abstract] [Full Text] [PDF]