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. 1992 May 1;99(5):771–793. doi: 10.1085/jgp.99.5.771

Diverse K+ channels in primary human T lymphocytes

PMCID: PMC2216619  PMID: 1376766

Abstract

We used patch clamp techniques to identify and characterize a variety of K+ channels in primary human peripheral T lymphocytes. The most common channel observed in cell-attached configuration was voltage gated and inactivating. In ensemble averages, the kinetics of its activation and inactivation were similar to those of the whole-cell, voltage-gated K+ current described previously (Cahalan, M. D., K. G. Chandy, T. E. DeCoursey, and S. Gupta. 1985. J. Physiol. [Lond.]. 358:197-237; Deutsch, C., D. Krause, and S. C. Lee. 1986. J. Physiol. [Lond.]. 372:405-423), suggesting that this channel underlies the major portion of the outward current in lymphocytes. A small fraction of the time, this or another very similar channel was observed to inactivate significantly more slowly. Another channel type observed in cell- attached recording was seen less frequently and was transient in its appearance. This channel has a unitary conductance of approximately 10 pS, similar to the voltage-gated channel, but its voltage-independent gating, lack of inactivation, and different kinetic parameters showed it to be distinct. In whole-cell recording there is often a significant plateau current during sustained depolarization. Experiments using whole-cell and excised outside-out configurations indicate that at least part of this residual current is carried by K+ and, as opposed to the predominant voltage-gated current, is charybdotoxin insensitive. These findings are consistent with evidence that implicates charybdotoxin-sensitive and -insensitive components in T lymphocyte proliferation and volume regulation.

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Selected References

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  1. Armstrong C. M., Bezanilla F. Charge movement associated with the opening and closing of the activation gates of the Na channels. J Gen Physiol. 1974 May;63(5):533–552. doi: 10.1085/jgp.63.5.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bezanilla F. A high capacity data recording device based on a digital audio processor and a video cassette recorder. Biophys J. 1985 Mar;47(3):437–441. doi: 10.1016/S0006-3495(85)83935-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Cahalan M. D., Lewis R. S. Role of potassium and chloride channels in volume regulation by T lymphocytes. Soc Gen Physiol Ser. 1988;43:281–301. [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. DeCoursey T. E. State-dependent inactivation of K+ currents in rat type II alveolar epithelial cells. J Gen Physiol. 1990 Apr;95(4):617–646. doi: 10.1085/jgp.95.4.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Decoursey T. E., Chandy K. G., Gupta S., Cahalan M. D. Two types of potassium channels in murine T lymphocytes. J Gen Physiol. 1987 Mar;89(3):379–404. doi: 10.1085/jgp.89.3.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Deutsch C., Krause D., Lee S. C. Voltage-gated potassium conductance in human T lymphocytes stimulated with phorbol ester. J Physiol. 1986 Mar;372:405–423. doi: 10.1113/jphysiol.1986.sp016016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Deutsch C., Lee S. C. Cell volume regulation in lymphocytes. Ren Physiol Biochem. 1988 May-Oct;11(3-5):260–276. doi: 10.1159/000173166. [DOI] [PubMed] [Google Scholar]
  11. Deutsch C., Lee S. C. Modulation of K+ currents in human lymphocytes by pH. J Physiol. 1989 Jun;413:399–413. doi: 10.1113/jphysiol.1989.sp017660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Deutsch C., Price M., Lee S., King V. F., Garcia M. L. Characterization of high affinity binding sites for charybdotoxin in human T lymphocytes. Evidence for association with the voltage-gated K+ channel. J Biol Chem. 1991 Feb 25;266(6):3668–3674. [PubMed] [Google Scholar]
  13. Deutsch C., Taylor J. S., Price M. pH homeostasis in human lymphocytes: modulation by ions and mitogen. J Cell Biol. 1984 Mar;98(3):885–893. doi: 10.1083/jcb.98.3.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fasolato C., Pozzan T. Effect of membrane potential on divalent cation transport catalyzed by the "electroneutral" ionophores A23187 and ionomycin. J Biol Chem. 1989 Nov 25;264(33):19630–19636. [PubMed] [Google Scholar]
  15. Fenwick E. M., Marty A., Neher E. A patch-clamp study of bovine chromaffin cells and of their sensitivity to acetylcholine. J Physiol. 1982 Oct;331:577–597. doi: 10.1113/jphysiol.1982.sp014393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fischmeister R., Ayer R. K., Jr, DeHaan R. L. Some limitations of the cell-attached patch clamp technique: a two-electrode analysis. Pflugers Arch. 1986 Jan;406(1):73–82. doi: 10.1007/BF00582957. [DOI] [PubMed] [Google Scholar]
  17. Gallin E. K. Ion channels in leukocytes. Physiol Rev. 1991 Jul;71(3):775–811. doi: 10.1152/physrev.1991.71.3.775. [DOI] [PubMed] [Google Scholar]
  18. Grinstein S., Dixon S. J. Ion transport, membrane potential, and cytoplasmic pH in lymphocytes: changes during activation. Physiol Rev. 1989 Apr;69(2):417–481. doi: 10.1152/physrev.1989.69.2.417. [DOI] [PubMed] [Google Scholar]
  19. Grinstein S., Smith J. D. Calcium-independent cell volume regulation in human lymphocytes. Inhibition by charybdotoxin. J Gen Physiol. 1990 Jan;95(1):97–120. doi: 10.1085/jgp.95.1.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Grissmer S., Cahalan M. D. Divalent ion trapping inside potassium channels of human T lymphocytes. J Gen Physiol. 1989 Apr;93(4):609–630. doi: 10.1085/jgp.93.4.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Holian A., Deutsch C. J., Holian S. K., Daniele R. P., Wilson D. F. Lymphocyte response to phytohemagglutinin: intracellular volume and intracellular [K+]. J Cell Physiol. 1979 Jan;98(1):137–144. doi: 10.1002/jcp.1040980115. [DOI] [PubMed] [Google Scholar]
  24. Horn R., Marty A. Muscarinic activation of ionic currents measured by a new whole-cell recording method. J Gen Physiol. 1988 Aug;92(2):145–159. doi: 10.1085/jgp.92.2.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ishida Y., Chused T. M. Heterogeneity of lymphocyte calcium metabolism is caused by T cell-specific calcium-sensitive potassium channel and sensitivity of the calcium ATPase pump to membrane potential. J Exp Med. 1988 Sep 1;168(3):839–852. doi: 10.1084/jem.168.3.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lee S. C., Deutsch C. Temperature dependence of K(+)-channel properties in human T lymphocytes. Biophys J. 1990 Jan;57(1):49–62. doi: 10.1016/S0006-3495(90)82506-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lee S. C., Price M., Prystowsky M. B., Deutsch C. Volume response of quiescent and interleukin 2-stimulated T-lymphocytes to hypotonicity. Am J Physiol. 1988 Feb;254(2 Pt 1):C286–C296. doi: 10.1152/ajpcell.1988.254.2.C286. [DOI] [PubMed] [Google Scholar]
  28. Lewis R. S., Cahalan M. D. Ion channels and signal transduction in lymphocytes. Annu Rev Physiol. 1990;52:415–430. doi: 10.1146/annurev.ph.52.030190.002215. [DOI] [PubMed] [Google Scholar]
  29. Lewis R. S., Cahalan M. D. Mitogen-induced oscillations of cytosolic Ca2+ and transmembrane Ca2+ current in human leukemic T cells. Cell Regul. 1989 Nov;1(1):99–112. doi: 10.1091/mbc.1.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lewis R. S., Cahalan M. D. Subset-specific expression of potassium channels in developing murine T lymphocytes. Science. 1988 Feb 12;239(4841 Pt 1):771–775. doi: 10.1126/science.2448877. [DOI] [PubMed] [Google Scholar]
  31. Mahaut-Smith M. P., Schlichter L. C. Ca2(+)-activated K+ channels in human B lymphocytes and rat thymocytes. J Physiol. 1989 Aug;415:69–83. doi: 10.1113/jphysiol.1989.sp017712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Marty A. Blocking of large unitary calcium-dependent potassium currents by internal sodium ions. Pflugers Arch. 1983 Feb;396(2):179–181. doi: 10.1007/BF00615524. [DOI] [PubMed] [Google Scholar]
  33. Matsuda H., Saigusa A., Irisawa H. Ohmic conductance through the inwardly rectifying K channel and blocking by internal Mg2+. Nature. 1987 Jan 8;325(7000):156–159. doi: 10.1038/325156a0. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Patlak J., Horn R. Effect of N-bromoacetamide on single sodium channel currents in excised membrane patches. J Gen Physiol. 1982 Mar;79(3):333–351. doi: 10.1085/jgp.79.3.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Price M., Lee S. C., Deutsch C. Charybdotoxin inhibits proliferation and interleukin 2 production in human peripheral blood lymphocytes. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10171–10175. doi: 10.1073/pnas.86.24.10171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ruppersberg J. P., Frank R., Pongs O., Stocker M. Cloned neuronal IK(A) channels reopen during recovery from inactivation. Nature. 1991 Oct 17;353(6345):657–660. doi: 10.1038/353657a0. [DOI] [PubMed] [Google Scholar]
  38. Ruppersberg J. P., Stocker M., Pongs O., Heinemann S. H., Frank R., Koenen M. Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation. Nature. 1991 Aug 22;352(6337):711–714. doi: 10.1038/352711a0. [DOI] [PubMed] [Google Scholar]
  39. Sands S. B., Lewis R. S., Cahalan M. D. Charybdotoxin blocks voltage-gated K+ channels in human and murine T lymphocytes. J Gen Physiol. 1989 Jun;93(6):1061–1074. doi: 10.1085/jgp.93.6.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. 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]
  42. Wilson H. A., Chused T. M. Lymphocyte membrane potential and Ca2+-sensitive potassium channels described by oxonol dye fluorescence measurements. J Cell Physiol. 1985 Oct;125(1):72–81. doi: 10.1002/jcp.1041250110. [DOI] [PubMed] [Google Scholar]
  43. Zagotta W. N., Aldrich R. W. Voltage-dependent gating of Shaker A-type potassium channels in Drosophila muscle. J Gen Physiol. 1990 Jan;95(1):29–60. doi: 10.1085/jgp.95.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]

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