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Science 306 (5700): 1374-1377

Copyright © 2004 by the American Association for the Advancement of Science

TRPM4 Regulates Calcium Oscillations After T Cell Activation

Pierre Launay,1*{dagger} Henrique Cheng,2*{ddagger} Subhashini Srivatsan,1 Reinhold Penner,2 Andrea Fleig,2 Jean-Pierre Kinet1§

Abstract: TRPM4 has recently been described as a calcium-activated nonselective (CAN) cation channel that mediates membrane depolarization. However, the functional importance of TRPM4 in the context of calcium (Ca2+) signaling and its effect on cellular responses are not known. Here, the molecular inhibition of endogenous TRPM4 in T cells was shown to suppress TRPM4 currents, with a profound influence on receptor-mediated Ca2+ mobilization. Agonist-mediated oscillations in intracellular Ca2+ concentration ([Ca2+]i), which are driven by store-operated Ca2+ influx, were transformed into a sustained elevation in [Ca2+]i. This increase in Ca2+ influx enhanced interleukin-2 production. Thus, TRPM4-mediated depolarization modulates Ca2+ oscillations, with downstream effects on cytokine production in T lymphocytes.

1 Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
2 Laboratory of Cell and Molecular Signaling, Center for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine at the University of Hawaii, Honolulu, HI 96813, USA.

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* These authors contributed equally to this work.

{dagger} Present address: INSERM E0225, Bichat Medical School, 75870 Paris Cedex 18, France.

{ddagger} Present address: All Children's Hospital and University of South Florida, 140 Seventh Avenue South, CRI 2012 St. Petersburg, FL 33701, USA.

§ To whom correspondence should be addressed. E-mail: jkinet{at}bidmc.harvard.edu

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