TRPM4 regulates calcium oscillations after T cell activation
TRPM4 regulates calcium oscillations after T cell activation
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DOI：
10.1126/science.1098845
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发表时间：
2004-11-19
期刊：
影响因子：
56.9
通讯作者：
Kinet, JP
中科院分区：
文献类型：
--
作者：
Launay, P;Cheng, H;Kinet, JP
TRPM4 最近被描述为介导膜去极化的钙激活非选择性 (CAN) 阳离子通道。然而，TRPM4 在钙 (Ca2+) 信号传导中的功能重要性及其对细胞反应的影响尚不清楚。在这里，T 细胞中内源性 TRPM4 的分子抑制被证明可以抑制 TRPM4 电流，对受体介导的 Ca2+ 动员产生深远影响。激动剂介导的细胞内 Ca2+ 浓度波动 ([Ca2+](i)) 是由钙池操纵的 Ca2+ 流入驱动的，转化为 [Ca2+](i) 的持续升高。 Ca2+ 流入的增加增强了白细胞介素 2 的产生。因此，TRPM4 介导的去极化调节 Ca2+ 振荡，并对 T 淋巴细胞中细胞因子的产生产生下游影响。
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 intracellutar 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.