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TRPM4 Regulates Calcium Oscillations After T Cell Activation
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 (Ca 2+ ) 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 Ca 2+ mobilization. Agonist-mediated oscillations in intracellular Ca 2+ concentration ([Ca 2+ ] i ), which are driven by store-operated Ca 2+ influx, were transformed into a sustained elevation in [Ca 2+ ] i . This increase in Ca 2+ influx enhanced interleukin-2 production. Thus, TRPM4-mediated depolarization modulates Ca 2+ oscillations, with downstream effects on cytokine production in T lymphocytes.
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Cited by
Molecular Basis of Calcium Signaling in Lymphocytes: STIM and ORAI
Hogan, P. G., Lewis, R. S., & Rao, A. (2010) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132550 · Cited by 760
The functional network of ion channels in T lymphocytes
Cahalan, M. D., & Chandy, K. G. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00816.x · Cited by 599
Trebak, M., & Kinet, J.-P. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-018-0110-7 · Cited by 508
Self-citationIon channels and transporters in lymphocyte function and immunity
Feske, S., Skolnik, E. Y., & Prakriya, M. (2012) · Nature Reviews Immunology · doi:10.1038/nri3233 · Cited by 441
Transient Receptor Potential Channels in the Vasculature
Earley, S., & Brayden, J. E. (2015) · Physiological Reviews · doi:10.1152/physrev.00026.2014 · Cited by 420
Metadata
- Authors
- Launay, P., Cheng, H., Srivatsan, S., Penner, R., Fleig, A., & Kinet, J.-P.
- Venue
- Science
- Published
- 2004-11-19
- Volume
- 306
- Issue
- 5700
- Pages
- 1374-1377
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1999934349
- Cited by
- 339
- References
- 0
- FWCI
- 7.82
- Type
- journal article
- Language
- en
- Open access
- closed
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- Launay, P., Cheng, H., Srivatsan, S., Penner, R., Fleig, A., & Kinet, J.-P. (2004). TRPM4 Regulates Calcium Oscillations After T Cell Activation. Science. https://doi.org/10.1126/science.1098845
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