Adhesion-Dependent Modulation of Macrophage K+ Channels

  • Margaret Colden-Stanfield
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 674)


Integrin-mediated adhesion of monocytes not only triggers cell rolling and diapedesis, it also activates ionic permeability changes resulting in monocyte activation, maturation and differentiation. Mononuclear phagocytes possess voltage-dependent inwardly rectifying K+ (Kir) currents and delayed outwardly, rectifying K+ (Kdr) currents that are modulated by tissue origin, adherence, presence of growth factors or cytokines and the functional or differentiation state of the cells. This chapter reviews the exploration of Kir and Kdr channels in mononuclear phagocytes over the last 30 years with an emphasis on culturing conditions, modulation by substrates and role in macrophage function. It has only been recent that successful attempts have been made to study these K+ currents in monocytes/macrophages as they may be engaged in the human body which may serve as the foundation for the development of novel therapeutic agents targeting macrophage Kir/Kdr channel activity to favorably influence risk factors for hypertension, atherosclerosis and diabetes.


Mononuclear Phagocyte Membr Biol American Physiological Society Brain Macrophage Early Signaling Event 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Gallin EK, Wiederhold M, Lipskey P et al. Spontaneous and induced membrane hyperpolarization in macrophages. J Cell Physol 1975; 86:653–662.CrossRefGoogle Scholar
  2. 2.
    Gallin EK, Gallin JJ. Interaction of chemotactic factors with human macrophages. Induction of transmembrane potential changes. J Cell Physiol 1977; 75:160–166.Google Scholar
  3. 3.
    Gallin EK, Livengood DR. Nonlinear current-voltage relationships in cultured macrophages. J Cell Biol 1980; 85(1):160–165.CrossRefPubMedGoogle Scholar
  4. 4.
    Gallin EK, Livengood DR. Inward rectification in mouse macrophages: evidence for a negative resistance region. Am J Physiol 1981; 241(1):C9–C17.PubMedGoogle Scholar
  5. 5.
    Gallin EK. Voltage clamp studies in macrophages from mouse spleen cultures. Science 1981; 214(4519):458–460.CrossRefPubMedGoogle Scholar
  6. 6.
    Gallin EK. Electrophysiological properties of macrophages. Fed Proc 1984; 43(9):2385–2389.PubMedGoogle Scholar
  7. 7.
    Gallin EK. Calcium-and voltage-activated potassium channels in human macrophages. Biophys J 1984; 46(6):821–825.CrossRefPubMedGoogle Scholar
  8. 8.
    Gallin EK. Ionic channels in leukocytes. J Leukoc Biol 1986; 39(3):241–254.PubMedGoogle Scholar
  9. 9.
    Gallin EK. Evidence for Ca-activated inwardly rectifying K+ channels in human macrophages. Am J Physiol 1989; 257(1 Pt 1):C77–C85.PubMedGoogle Scholar
  10. 10.
    Gallin EK. Ion channels in leukocytes. Physiol Rev 1991; 71(3):775–811.Google Scholar
  11. 11.
    Gallin EK, McKinney LC. Patch-clamp studies in human macrophages: single-channel and whole-cell characterization of two K+ conductances. J Membr Biol 1988; 103(1):55–66.CrossRefPubMedGoogle Scholar
  12. 12.
    Gallin EK, Grinstein S. Ion channels and carriers in leukocytes: distribution and functional role. In: Gallin JI, Goldstein IM and R. Snyderman, eds. Inflammation: Basic Principles and Clinical Correlates, Second Edition; New York: Raven Press, Ltd, 1992:441–458.Google Scholar
  13. 13.
    Nelson DJ, Jow B, Popovich KJ. Whole-cell currents in macrophages: II. Alveolar macrophages. J Membr Biol 1990; 117(1):45–55.CrossRefPubMedGoogle Scholar
  14. 14.
    Nelson DJ, Jow B, Jow F. Lipopolysaccharide induction of outward potassium current expression in human monocyte-derived macrophages: lack of correlation with secretion. J Membr Biol 1992; 125(3):207–218.PubMedGoogle Scholar
  15. 15.
    McCann FV, Keller TM, Guyre PM. Ion channels in human macrophages compared with the U-937 cell line. J Membr Biol 1987; 96(1):57–64.CrossRefPubMedGoogle Scholar
  16. 16.
    Gallin EK, Sheehy PA. Differential expression of inward and outward potassium currents in the macrophage-like cell line J774.1. J Physiol 1985; 369:475–499.PubMedGoogle Scholar
  17. 17.
    Randriamampita C, Trautmann A. Ionic channels in murine macrophages. J Cell Biol 1987; 105(2):761–769.CrossRefPubMedGoogle Scholar
  18. 18.
    McKinney LC, Gallin EK. Inwardly rectifying whole-cell and single-channel K+ currents in the murine macrophage cell line J774.1. J Membr Biol 1988; 103(1):41–53.CrossRefPubMedGoogle Scholar
  19. 19.
    McKinney LC, Gallin EK. Effect of adherence, cell morphology and lipopolysaccharide on potassium conductance and passive membrane properties of murine macrophage J774.1 cells. J Membr Biol 1990; 116(1):47–56.CrossRefPubMedGoogle Scholar
  20. 20.
    McKinney LC, Gallin EK. G-protein activators induce a potassium conductance in murine macrophages. J Membr Biol 1992; 130(3):265–276.PubMedGoogle Scholar
  21. 21.
    Judge SI, Montcalm-Mazzilli E, Gallin EK. IKir regulation in murine macrophages: whole cell and perforated patch studies. Am J Physiol 1994; 267(6 Pt 1):C1691–C1698.PubMedGoogle Scholar
  22. 22.
    Forero ME, Marín M, Corrales Am et al. Leishmania amazonensis infection induces changes in the electrophysiological properties of macrophage-like cells. J Membr Biol 1999; 170(2):173–180.CrossRefPubMedGoogle Scholar
  23. 23.
    Gerth A, Grosche J, Nieber K et al. Intracellular LPS inhibits the activity of potassium channels and fails to activate NFkappaB in human macrophages. J Cell Physiol 2005; 202(2):442–452.CrossRefPubMedGoogle Scholar
  24. 24.
    Perier F, Coulter KL, Radeke CM et al. Expression of an inwardly rectifying potassium channel in xenopus oocytes. J Neurochem 1992; 59:1971–1974.CrossRefPubMedGoogle Scholar
  25. 25.
    Kubo Y, Baldwin TJ, Jan YN et al. Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature 1993; 362(6416):127–133.CrossRefPubMedGoogle Scholar
  26. 26.
    Sundström C, Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer 1976; 17(5):565–577.CrossRefGoogle Scholar
  27. 27.
    Collins SJ, Ruscetti FW, Gallagher RE et al. Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci USA 1978; 75(5):2458–2462.CrossRefPubMedGoogle Scholar
  28. 28.
    Auwerx, J. The human leukemia cell line, THP-1: A multifacetted model for the study of monocyte-macrophage differentiation. Experientia 1991; 47:22–31.CrossRefPubMedGoogle Scholar
  29. 29.
    Wieland SJ, Chou RH, Gong QH. Macrophage-colony-stimulating factor (CSF-1) modulates a differentiation-specific inward-rectifying potassium current in human leukemic (HL-60) cells. J Cell Physiol 1990; 142(3):643–651.CrossRefPubMedGoogle Scholar
  30. 30.
    Kim SY, Silver MR, DeCoursey TE. Ion channels in human THP-1 monocytes. J Membr Biol 1996; 152(2):117–130.CrossRefPubMedGoogle Scholar
  31. 31.
    DeCoursey TE, Kim SY, Silver MR et al. Ion channel expression in PMA-differentiated human THP-1 macrophages. J Membr Biol 1996; 152(2):141–157.CrossRefPubMedGoogle Scholar
  32. 32.
    Colden-Stanfield M, Gallin EK. Modulation of K+ currents in monocytes by VCAM-1 and E-selectin on activated human endothelium. Am J Physiol Cell Physiol 1998; 275(1 Pt 1):C267–C277.Google Scholar
  33. 33.
    Colden-Stanfield M. Clustering of very late antigen-4 integrins modulates K+ currents to alter Ca2+-mediated monocyte function. Am J Physiol Cell Physiol 2002; 283(3):C990–C1000.PubMedGoogle Scholar
  34. 34.
    Colden-Stanfield M, Scanlon M. VCAM-1-induced inwardly rectifying K+ current enhances Ca2+ entry in human THP-1 monocytes. Am J Physiol Cell Physiol 2000; 279(2):C488–C494.PubMedGoogle Scholar
  35. 35.
    Eder C, Fischer HG. Effects of colony-stimulating factors on voltage-gated K+ currents of bone marrow-derived macrophages. Naunyn Schmiedebergs Arch Pharmacol 1997; 355(2):198–202.CrossRefPubMedGoogle Scholar
  36. 36.
    Vicente R, Escalada A, Coma M et al. Differential voltage-dependent K+ channel responses during proliferation and activation in macrophages. J Biol Chem 2003; 278(47):46307–46320. Epub 2003. Erratum in: J Biol Chem 2005; 280(13):13204.CrossRefPubMedGoogle Scholar
  37. 37.
    Kettenmann H, Hoppe D, Gottmann K et al. Cultured microglial cells have a distinct pattern of membrane channels different from peritoneal macrophages. J Neurosci Res 1990; 26(3):278–287.CrossRefPubMedGoogle Scholar
  38. 38.
    Kettenmann H, Banati R, Walz W. Electrophysiological behavior of microglia. Glia 1993; 7(1):93–101.CrossRefPubMedGoogle Scholar
  39. 39.
    Korotzer AR, Cotman CW. Voltage-gated currents expressed by rat microglia in culture. Glia 1992; 6(2):81–88.CrossRefPubMedGoogle Scholar
  40. 40.
    Eder C. Ion channels in microglia (brain macrophages). Am J Physiol 1998; 275(2 Pt 1):C327–C342.PubMedGoogle Scholar
  41. 41.
    Ilschner S, Ohlemeyer C, Gimpl G et al. Modulation of potassium currents in cultured murine microglial cells by receptor activation and intracellular pathways. Neuroscience 1995; 66(4):983–1000.CrossRefPubMedGoogle Scholar
  42. 42.
    Fischer HG, Eder C, Hadding U et al. Cytokine-dependent K+ channel profile of microglia at immunologically defined functional states. Neuroscience 1995; 64(1):183–191.CrossRefPubMedGoogle Scholar
  43. 43.
    Schlichter L, Sidell N, Hagiwara S. Potassium channels mediate killing by human natural killer cells. Proc Natl Acad Sci USA 1986; 83(2):451–455.CrossRefPubMedGoogle Scholar
  44. 44.
    Küst B, Buttini M, Sauter A et al. K+-channels and cytokines as markers for microglial activation. Adv Exp Med Biol 1997; 429:109–117.PubMedGoogle Scholar
  45. 45.
    Chung S, Jung W, Lee MY. Inward and outward rectifying potassium currents set membrane potentials in activated rat microglia. Neurosci Lett 1999; 262(2):121–124.CrossRefPubMedGoogle Scholar
  46. 46.
    McCloskey MA, Qian YX. Selective expression of potassium channels during mast cell differentiation. J Biol Chem 1994; 269:14813–14819.PubMedGoogle Scholar
  47. 47.
    Maltsev VA, Wobus AM, Rohwedel J et al. Cardiomyocytes differentiated in vitro from embryonic stem cells developmentally express cardiac-specific genes and ionic currents. Circ Res 1994; 75:233–244.PubMedGoogle Scholar
  48. 48.
    Shin KS, Park J, Kwon J et al. A possible role of inwardly rectifying K+ channels in chick myoblast differentiation. Am J Physiol 1997; 272 (Cell Physiol 41):C894–C900.PubMedGoogle Scholar
  49. 49.
    Hu Q, Shi YL. Characterization of an inwardly rectifying potassium current in NG108-15 neuroblastoma x glioma cells. Pflugers Arch 1997; 433:617–625.CrossRefPubMedGoogle Scholar
  50. 50.
    Gerrity RG. The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol 1981; 103(2):181–190.PubMedGoogle Scholar
  51. 51.
    Lei XJ, Ma AQ, Xi YT et al. Expression of Kir2.1 channel during differentiation of human macrophages into foam cells. Di Yi Jun Yi Da Xue Xue Bao 2005; 25(12):1461–1467.PubMedGoogle Scholar
  52. 52.
    Lei XJ, Ma AQ, Xi YT et al. Inhibition of human macrophage-derived foam cell differentiation by blocking Kv1.3 and kir2.1 channels. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2006; 31(4):493–498.PubMedGoogle Scholar
  53. 53.
    Lei XJ, Ma AQ, Xi YT et al. Inhibitory effects of blocking voltage-dependent potassium channel 1.3 on human monocyte-derived macrophage differentiation into foam cells. Beijing Da Xue Xue Bao 2006; 38(3):257–261.PubMedGoogle Scholar
  54. 54.
    Ypey DL, Clapham DE. Development of a delayed outward-rectifying K+ conductance in cultured mouse peritoneal macrophages. Proc Natl Acad Sci USA 1984; 81(10):3083–3087.CrossRefGoogle Scholar
  55. 55.
    Chung S, Joe E, Soh H et al. Delayed rectifier potassium currents induced in activated rat microglia set the resting membrane potential. Neurosci Lett 1998; 242(2):73–76.CrossRefPubMedGoogle Scholar
  56. 56.
    Visentin S, Agresti C, Patrizio M et al. Ion channels in rat microglia and their different sensitivity to lipopolysaccharide and interferon-gamma. J Neurosci Res 1995; 42(4):439–451.CrossRefPubMedGoogle Scholar
  57. 57.
    Sievers J, Schmidtmayer J, P arwaresch R. Blood monocytes and spleen macrophages differentiate into microglia-like cells when cultured on astrocytes. Ann Anat 1994; 176(1):45–51.PubMedGoogle Scholar
  58. 58.
    Ince C, Coremans JM, Ypey DL et al. Phagocytosis by human macrophages is accompanied by changes in ionic channel currents. J Cell Biol 1988; 106(6):1873–1878.CrossRefPubMedGoogle Scholar
  59. 59.
    Pannasch U, Färber K, Nolte C et al. The potassium channels Kv1.5 and Kv1.3 modulate distinct functions of microglia. Mol Cell Neurosci 2006; 33(4):401–411. Epub, 2006.CrossRefPubMedGoogle Scholar
  60. 60.
    Nutile-McMenemy N, Elfenbein A, DeLo JA. Minocycline decreases in vitro microglial motility, β1-integrin and Kv1.3 channel expression. J Neurochem 2007; 103:2035–2046.CrossRefPubMedGoogle Scholar
  61. 61.
    Vicente R, Escalada A, Soler C et al. Pattern of kv beta subunit expression in macrophages depends upon proliferation and the mode of activation. J Immunol 2005; 174(8):4736–4744.PubMedGoogle Scholar
  62. 62.
    Vicente R, Escalada A, Villalonga N et al. Association of kv1.5 and kv1.3 contributes to the major voltage-dependent K+ channel in macrophages. J Biol Chem 2006; 281(49):37675–37685. Epub, 2006.CrossRefPubMedGoogle Scholar
  63. 63.
    Vicente R, Villalonga N, Calvo M et al. Kv1.5 association modifies kv1.3 traffic and membrane localization. J Biol Chem 2008; 283(13):8756–8764. Epub, 2008.CrossRefPubMedGoogle Scholar
  64. 64.
    Villalonga N, Escalada A, Vicente R et al. Kv1.3/kv1.5 heteromeric channels compromise pharmacological responses in macrophages. Biochem Biophys Res Commun 2007; 352(4):913–918. Epub, 2006.CrossRefPubMedGoogle Scholar
  65. 65.
    Elbashir SM, Harborth J, Lendeckel W et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001; 24; 411(6836):494–498.CrossRefGoogle Scholar
  66. 66.
    Elbashir SM, Lendeckel W, Tuschl T. RNA interference is mediated by 21-and 22-nucleotide RNAs. Genes Dev 2001; 15(2):188–200.CrossRefPubMedGoogle Scholar
  67. 67.
    Feral CC, Neels JG, Kummer C et al. Blockade of α4 integrin signaling ameliorates the metabolic consequences of high fat diet-induced obesity. Diabetes 2008; 57(7):1842–1851.CrossRefPubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Department of PhysiologyMorehouse School of MedicineAtlantaUSA

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