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. 1986 Aug;83(15):5625–5629. doi: 10.1073/pnas.83.15.5625

K channels are expressed early in human T-cell development.

L Schlichter, N Sidell, S Hagiwara
PMCID: PMC386341  PMID: 2426701

Abstract

Mature human T lymphocytes proliferate in response to the mitogen phytohemagglutinin (PHA), but immature thymocytes lacking the T3 receptor (T3- thymocytes) do not. Because functioning K channels are required for proliferation of mature T cells, we asked whether immunoincompetent T3- thymocytes lack normal K channels. We report that T3- thymocytes have a K+ current similar to that of mature peripheral T cells--that is, similar voltage dependence, activation and inactivation kinetics, and pharmacology. Moreover, the maximal specific K+ conductance is the same for both cell types, implying a similar density of activable channels in each cell. In assessing the functional responses of the channels to PHA, we found that the K+ current of immature and mature cells responds similarly to the mitogen. Responses near the threshold voltage for activating the K+ current were variable; the K+ conductance and rate of activation were increased, decreased, or unchanged after PHA treatment. For several cells, the voltage dependence of the conductance and activation kinetics was shifted in opposite directions. At more positive voltages, PHA consistently caused a 10-20% suppression of conductance that was not due to the addition of an inward current, to changes in the time course of activation or inactivation, or to changes in the steady-state level of inactivation. The effects of PHA on the K+ current cannot be explained by a simple shift in surface potential, as has been hypothesized to be involved in its triggering of T-cell proliferation. Taken together, our findings show K channels are expressed very early in T-cell differentiation, possibly before thymic processing, differential responses of the K+ current to PHA do not account for the failure of T3- thymocytes to proliferate, and changes in surface potential are probably not a necessary early event in activation of T cells by PHA.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bregestovski P., Redkozubov A., Alexeev A. Elevation of intracellular calcium reduces voltage-dependent potassium conductance in human T cells. 1986 Feb 27-Mar 5Nature. 319(6056):776–778. doi: 10.1038/319776a0. [DOI] [PubMed] [Google Scholar]
  2. Cahalan M. D., Chandy K. G., DeCoursey T. E., Gupta S. A voltage-gated potassium channel in human T lymphocytes. J Physiol. 1985 Jan;358:197–237. doi: 10.1113/jphysiol.1985.sp015548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chandy K. G., DeCoursey T. E., Cahalan M. D., McLaughlin C., Gupta S. Voltage-gated potassium channels are required for human T lymphocyte activation. J Exp Med. 1984 Aug 1;160(2):369–385. doi: 10.1084/jem.160.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DeCoursey T. E., Chandy K. G., Gupta S., Cahalan M. D. Voltage-gated K+ channels in human T lymphocytes: a role in mitogenesis? Nature. 1984 Feb 2;307(5950):465–468. doi: 10.1038/307465a0. [DOI] [PubMed] [Google Scholar]
  5. Fernandez J. M., Fox A. P., Krasne S. Membrane patches and whole-cell membranes: a comparison of electrical properties in rat clonal pituitary (GH3) cells. J Physiol. 1984 Nov;356:565–585. doi: 10.1113/jphysiol.1984.sp015483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fukushima Y., Hagiwara S., Henkart M. Potassium current in clonal cytotoxic T lymphocytes from the mouse. J Physiol. 1984 Jun;351:645–656. doi: 10.1113/jphysiol.1984.sp015268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hagiwara S., Ohmori H. Studies of calcium channels in rat clonal pituitary cells with patch electrode voltage clamp. J Physiol. 1982 Oct;331:231–252. doi: 10.1113/jphysiol.1982.sp014371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  9. Hesketh T. R., Bavetta S., Smith G. A., Metcalfe J. C. Duration of the calcium signal in the mitogenic stimulation of thymocytes. Biochem J. 1983 Aug 15;214(2):575–579. doi: 10.1042/bj2140575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Matteson D. R., Deutsch C. K channels in T lymphocytes: a patch clamp study using monoclonal antibody adhesion. Nature. 1984 Feb 2;307(5950):468–471. doi: 10.1038/307468a0. [DOI] [PubMed] [Google Scholar]
  11. Oettgen H. C., Terhorst C., Cantley L. C., Rosoff P. M. Stimulation of the T3-T cell receptor complex induces a membrane-potential-sensitive calcium influx. Cell. 1985 Mar;40(3):583–590. doi: 10.1016/0092-8674(85)90206-5. [DOI] [PubMed] [Google Scholar]
  12. Reinherz E. L., Penta A. C., Hussey R. E., Schlossman S. F. A rapid method for separating functionally intact human T lymphocytes with monoclonal antibodies. Clin Immunol Immunopathol. 1981 Nov;21(2):257–266. doi: 10.1016/0090-1229(81)90214-2. [DOI] [PubMed] [Google Scholar]
  13. Schlichter L., Sidell N., Hagiwara S. Potassium channels mediate killing by human natural killer cells. Proc Natl Acad Sci U S A. 1986 Jan;83(2):451–455. doi: 10.1073/pnas.83.2.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sidell N., Famatiga E., Golub S. H. Augmentation of human thymocyte proliferative responses by retinoic acid. Exp Cell Biol. 1981;49(5):239–245. doi: 10.1159/000163828. [DOI] [PubMed] [Google Scholar]
  15. Trinchieri G., Perussia B. Human natural killer cells: biologic and pathologic aspects. Lab Invest. 1984 May;50(5):489–513. [PubMed] [Google Scholar]
  16. Tsien R. Y., Pozzan T., Rink T. J. T-cell mitogens cause early changes in cytoplasmic free Ca2+ and membrane potential in lymphocytes. Nature. 1982 Jan 7;295(5844):68–71. doi: 10.1038/295068a0. [DOI] [PubMed] [Google Scholar]
  17. Umiel T., Daley J. F., Bhan A. K., Levey R. H., Schlossman S. F., Reinherz E. L. Acquisition of immune competence by a subset of human cortical thymocytes expressing mature T cell antigens. J Immunol. 1982 Sep;129(3):1054–1060. [PubMed] [Google Scholar]
  18. Ypey D. L., Clapham D. E. Development of a delayed outward-rectifying K+ conductance in cultured mouse peritoneal macrophages. Proc Natl Acad Sci U S A. 1984 May;81(10):3083–3087. doi: 10.1073/pnas.81.10.3083. [DOI] [PMC free article] [PubMed] [Google Scholar]

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