T-CELL MITOGENS CAUSE EARLY CHANGES IN CYTOPLASMIC FREE CA(2+) AND MEMBRANE-POTENTIAL IN LYMPHOCYTES
T-CELL MITOGENS CAUSE EARLY CHANGES IN CYTOPLASMIC FREE CA(2+) AND MEMBRANE-POTENTIAL IN LYMPHOCYTES
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DOI：
10.1038/295068a0
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发表时间：
1982-01-01
期刊：
影响因子：
64.8
通讯作者：
RINK, TJ
中科院分区：
文献类型：
--
作者：
TSIEN, RY;POZZAN, T;RINK, TJ
研究哺乳动物细胞生长和增殖控制的最佳模型之一是淋巴细胞对刺激生长、DNA合成和分裂的促有丝分裂剂1 -4的反应。有丝分裂原如何工作仍然不清楚，尽管已经假设它们增加细胞质游离钙[Ca 2 +]i，作为增殖所必需的细胞内过程级联的触发剂3 -6。然而，淋巴细胞[Ca ~（2+）] i以前无法测量。一种新的技术7将一种新的钙离子特异性指示剂8装载到完整的小细胞的细胞质中，现在已经有可能在小鼠胸腺细胞和猪淋巴结淋巴细胞中首次直接测量[Ca 2 +] i。我们在这里表明，已知的凝集素刺激T细胞提高平均[Ca 2 +] 1大约在几分钟内的两倍。外部Ca ~（2+）的降低或环AMP的升高（已知抑制有丝分裂的条件）阻止了[Ca ~（2+）] i反应。[Ca 2 +] i的升高伴随着膜电位的超极化，这显然是由于Ca 2+激活的K+电导。共致癌物12-0-tetradecanoylphorbol-13-acetate（TPA）似乎刺激通常由Ca 2+激活的细胞功能。
One of the best models for studying the control of mammalian cell growth and proliferation is the response of lymphocytes to mitogenic agents1–4, which stimulate growth, DNA synthesis and division. How mitogens work remains obscure, although it has been hypothesized that they increase cytoplasmic free calcium, [Ca2+]i, as a trigger for the cascade of intracellular processes necessary for proliferation3–6. However, lymphocyte [Ca2+]ihas not previously been measurable. A new technique7for loading a novel Ca2+-specific indicator8into the cytoplasm of intact small cells has now made possible the first direct measurements of [Ca2+]iin mouse thymocytes and pig node lymphocytes. We show here that lectins known to stimulate T cells raise average [Ca2+]1approximately twofold within a few minutes. Deprivation of external Ca2+or elevation of cyclic AMP, conditions known to inhibit mitogenesis, prevented the [Ca2+]iresponse. Rises in [Ca2+]iwere accompanied by hyper-polarization of the membrane potential, apparently due to a Ca2+-activated K+conductance. The co-carcinogen 12-0-tetradecanoylphorbol-13-acetate (TPA) seems to stimulate cell functions normally activated by Ca2+.