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T-cell mitogens cause early changes in cytoplasmic free Ca2+ and membrane potential in lymphocytes

Nature volume 295, pages 68–71 (1982)Cite this article

Abstract

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+]i has not previously been measurable. A new technique7 for loading a novel Ca2+-specific indicator8 into the cytoplasm of intact small cells has now made possible the first direct measurements of [Ca2+]i in mouse thymocytes and pig node lymphocytes. We show here that lectins known to stimulate T cells raise average [Ca2+]1 approximately twofold within a few minutes. Deprivation of external Ca2+or elevation of cyclic AMP, conditions known to inhibit mitogenesis, prevented the [Ca2+]i response. Rises in [Ca2+]i were 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+.

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Author notes

  1. R. Y. Tsien

    Present address: Department of Physiology-Anatomy, University of California, Berkeley, California, 94720, USA

  2. T. Pozzan: Istituto di Patologia Generale, Via Loredan 16, 35100 Padova, Italy

Authors and Affiliations

  1. Physiological Laboratory, University of Cambridge, Cambridge, CB2 3EG, UK

    R. Y. Tsien, T. Pozzan & T. J. Rink

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  3. T. J. Rink
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Tsien, R., Pozzan, T. & Rink, T. T-cell mitogens cause early changes in cytoplasmic free Ca2+ and membrane potential in lymphocytes. Nature 295, 68–71 (1982). https://doi.org/10.1038/295068a0

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