Skip to main content
SpringerLink
Log in

Properties of voltage-gated currents of microglia developed using macrophage colony-stimulating factor

  • Original Article
  • Molecular and Cellular Physiology
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

Microglia were isolated from a murine neonatal brain cell culture in which their development had been stimulated by supplementation with the macrophage/microglial growth factor macrophage colony-stimulating factor (M-CSF). Using the whole-cell configuration of the patch-clamp technique, voltage-gated membrane currents were recorded from these microglial cells. Hyperpolarization induced inward rectifying K+ currents, as described for microglia from untreated cultures. These currents activated negative to the K+ equilibrium potential and, with a strong hyperpolarization, displayed time-dependent inactivation. The inactivation was abolished when extracellular NaCl was replaced by N-methyl-d-glucamine (NMG), thereby indicating a partial block of this K+ conductance by Na+. Inward rectifying currents were also blocked by extracellularly applied Cs+ or Ba2+. They were slightly diminished following treatment with extracellular tetraethylammonium chloride (TEA) but were not affected by 4-aminopyridine (4-AP). Upon long lasting depolarizing voltage pulses to potentials positive to 0 mV, the cells exhibited a slowly activating H+ current which could be reduced by application of inorganic polyvalent cations (Ba2+, Cd2+, Co2+, La3+, Ni2+, Zn2+) as well as by 4-AP or TEA. Based on their kinetics and pharmacological characteristics, both currents detected on M-CSF-grown microglia are suggested to correspond to the inward rectifier and the H+ current of macrophages.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barish ME, Baud C (1984) A voltage-gated hydrogen ion current in the oocyte membrane of the axolotl, Ambystoma. J Physiol (Lond) 352:243–263

    Google Scholar 

  2. Byerly L, Meech R, Moody W (1984) Rapidly activating hydrogen ion currents in perfused neurones of the snail, lymnaea stagnalis. J Physiol (Lond) 351:199–216

    Google Scholar 

  3. DeCoursey TE (1991) Hydrogen ion currents in rat alveolar epithelial cells. Biophys J 60:1243–1253

    PubMed  Google Scholar 

  4. Demaurex N, Grinstein S, Jaconi M, Schlegel W, Lew DP, Krause KH (1993) Proton currents in human granulocytes: regulation by membrane potential and intracellular pH. J Physiol (Lond) 466:329–344

    Google Scholar 

  5. Fischer HG, Bielinsky AK, Nitzgen B, Däubener W, Hadding U (1993) Functional dichotomy of mouse microglia developed in vitro: differential effects of macrophage and granulocyte/macrophage colony-stimulating factor on cytokine secretion and antitoxoplasmic activity. J Neuroimmunol 45:193–202

    Article  PubMed  Google Scholar 

  6. Fischer HG, Eder C, Hadding U, Heinemann U (1995) Cytokine-dependent K+ channel profile of microglia at immunologically defined functional states. Neuroscience 64:183–191

    Article  PubMed  Google Scholar 

  7. Frei K, Siepl C, Groscurth P, Bodmer S, Fontana A (1988) Immunobiology of microglial cells. Ann NY Acad Sci 540:218–227

    PubMed  Google Scholar 

  8. Gallin EK (1991) Ion channels in leukocytes. Physiol Rev 71:775–811

    PubMed  Google Scholar 

  9. Gallin EK, McKinney LC (1988) Patch-clamp studies in human macrophages: single-channel and whole-cell characterization of two K+ conductances. J Membr Biol 103:55–66

    PubMed  Google Scholar 

  10. Gallin EK, Sheehy PA (1985) Differential expression of inward and outward potassium currents in the macrophage-like cell line J774.1. J Physiol (Lond) 369:475–499

    Google Scholar 

  11. Gay LA, Stanfield PR (1977) Cs+ causes a voltage-dependent block of inward K currents in resting skeletal muscle fibers. Nature 267:169–170

    Google Scholar 

  12. Giulian D (1987) Ameboid microglia as effectors of inflammation in the nervous system. J Neurosci Res 18:155–171

    PubMed  Google Scholar 

  13. Giulian D, Ingeman JE (1988) Colony-stimulating factors as promotors of ameboid microglia. J Neurosci 12:4707–4717

    Google Scholar 

  14. Hagiwara S, Miyazaki S, Moody W, Patlak J (1978) Blocking effect of barium and hydrogen ions on the potassium current during anomalous rectification in the starfish egg. J Physiol (Lond) 279:167–185

    Google Scholar 

  15. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391:85–100

    Google Scholar 

  16. Hao C, Guilbert LJ, Fedoroff S (1990) Production of colony-stimulating factor-1 (CSF-1) by mouse astroglia in vitro. J Neurosci Res 27:314–323

    PubMed  Google Scholar 

  17. Hao C, Richardson A, Fedoroff S (1991) Macrophage-like cells originate from neuroepithelium in culture: characterization and properties of the macrophage-like cells. Int J Dev Neurosci 9:1–14

    Article  PubMed  Google Scholar 

  18. Kanno T, Takishima T (1990) Chloride and potassium channels in U937 human monocytes. J Membr Biol 116:149–161

    PubMed  Google Scholar 

  19. Kapus A, Romanek R, Qu AY, Rotstein OD, Grinstein S (1993) A pH-sensitive and voltage-dependent proton conductance in the plasma membrane of macrophages. J Gen Physiol 102:729–760

    Article  PubMed  Google Scholar 

  20. Kettenmann H, Hoppe D, Gottmann K, Banati R, Kreutzberg G (1990) Cultured microglial cells have a distinct pattern of membrane channels different from peritoneal macrophages. J Neurosci Res 26:278–287

    PubMed  Google Scholar 

  21. Kolb HA (1990) Potassium channels in excitable and non-excitable cells. Rev Physiol Biochem Pharmacol 115:51–91

    PubMed  Google Scholar 

  22. Krautwald S, Baccarini M (1993) Bacterially expressed murine CSF-1 possesses agonistic activity in its monomeric form. Biochem Biophys Res Commun 192:720–727

    Article  PubMed  Google Scholar 

  23. Kubo Y, Baldwin TJ, Jan YN, Jan LY (1993) Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature 362:127–133

    Article  PubMed  Google Scholar 

  24. Ling EA, Penney D, Leblond CP (1980) Use of carbon labeling to demonstrate the role of blood monocytes as precursors of “ameboid cells” present in the corpus callosum of postnatal rats. J Comp Neurol 193:631–657

    PubMed  Google Scholar 

  25. Lukacs GL, Kapus A, Nanda A, Romanek R, Grinstein S (1993) Proton conductance of the plasma membrane: properties, regulation, and functional role. Am J Physiol 265:C3-C14

    PubMed  Google Scholar 

  26. Mahaut-Smith MP (1989) The effect of zinc on calcium and hydrogen ion currents in intact snail neurones. J Exp Biol 145:455–466

    Google Scholar 

  27. McKinney LC, Gallin EK (1988) Inwardly rectifying whole-cell and single-channel K currents in the murine macrophage cell line J774.1. J Membr Biol 103:41–53

    PubMed  Google Scholar 

  28. Meech RW, Thomas RC (1987) Voltage-dependent intracellular pH in Helix aspersa neurones. J Physiol (Lond) 390:433–452

    Google Scholar 

  29. Nelson DJ, Jow B, Jow F (1990) Whole-cell currents in macrophages:I. Human monocyte-derived macrophages. J Membr Biol 117:29–44

    PubMed  Google Scholar 

  30. Nörenberg W, Gebicke-Härter PJ, Illes P (1994) Voltage-dependent potassium channels in activated rat microglia. J Physiol (Lond) 475:15–32

    Google Scholar 

  31. Perry VH, Gordon S (1988) Macrophages and microglia in the nervous system. Trends Neurosci 11:273–277

    Article  PubMed  Google Scholar 

  32. Piani D, Spranger M, Frei K, Schaffner A, Fontana A (1992) Macrophage-induced cytotoxicity of N-methyl-D-aspartate receptor positive neurons involves excitatory amino acids rather than reactive oxygen intermediates and cytokines. Eur J Immunol 22:2429–2436

    PubMed  Google Scholar 

  33. Rajavashisth TB, Eng R, Shadduck RK, Waheed A, Ben-Avram CM, Shively JE, Lusis AJ (1987) Cloning and tissue-specific expression of mouse macrophage colony-stimulating factor mRNA. Proc Natl Acad Sci USA 84:1157–1161

    PubMed  Google Scholar 

  34. Randriamampita C, Trautmann A (1987) Ionic channels in murine macrophages. J Cell Biol 105:761–769

    Article  PubMed  Google Scholar 

  35. Rudy B (1988) Diversity and ubiquity of K channels. Neuroscience 25:729–749

    Article  PubMed  Google Scholar 

  36. Standen NB, Stanfield PR (1978) A potential- and time-dependent blockade of inward rectification in frog skeletal muscle fibers by barium and strontium ions. J Physiol 280:169–191

    PubMed  Google Scholar 

  37. Standen NB, Stanfield PR (1979) Potassium depletion and sodium block of potassium currents under hyperpolarization in frog sartorius muscle. J Physiol (Lond) 294:497–520

    Google Scholar 

  38. Stanley ER, Head PM (1977) Factors regulating macrophage production and growth. J Biol Chem 252:4305–4312

    PubMed  Google Scholar 

  39. Théry C, Hétier E, Evrard C, Mallat M (1990) Expression of macrophage colony-stimulating factor gene in the mouse brain during development. J Neurosci Res 26:129–133

    PubMed  Google Scholar 

  40. Wieland SJ, Chou RH, Gong QH (1990) Macrophage-colony-stimulating factor (CSF-1) modulates a differntiation-specific inward-rectifying potassium current in human leukemic (HL-60) cells. J Cell Physiol 142:643–651

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Neurophysiologie, Zentrum für Physiologie und Pathophysiologie, Universität zu Köln, Robert-Koch-Strasse 39, D-50931, Köln, Germany

    Claudia Eder

  2. Institut für Medizinische Mikrobiologie und Virologie, Heinrich-Heine-Universität, Universitätsstrasse 1, D-40225, Düsseldorf, Germany

    Hans -Georg Fischer & Ulrich Hadding

  3. Abt. Neurophysiologie, Institut für Physiologie der Charité, Humboldt Universität, Tucholsky Strasse 2, D-10117, Berlin, Germany

    Claudia Eder & Uwe Heinemann

Authors
  1. Claudia Eder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hans -Georg Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ulrich Hadding
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Uwe Heinemann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eder, C., Fischer, H.G., Hadding, U. et al. Properties of voltage-gated currents of microglia developed using macrophage colony-stimulating factor. Pflugers Arch. 430, 526–533 (1995). https://doi.org/10.1007/BF00373889

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00373889

Key words

Search

Navigation