Potassium Channel Blockers Tetraethylammonium and 4-Aminopyridine Fail to Prevent Microglial Activation Induced by Elevated Potassium Concentration
Abstract
The effect of potassium channel blockers tetraethylammonium and 4-aminopyridine was examined on the elevated K+ concentration-induced microglial activation on rat hippocampal slice preparations. Microglial cells were detected by immunohistochemistry with a monoclonal antibody (OX 42) raised against a type 3 complement receptor. During activation the morphology of the microglial cells changes and the staining intensity increases. The degree of microglial activation was determined by measuring the integrated optical density of the cells. Tetraethylammonium and 4-aminopyridine failed to reduce the elevated K+ concentration-induced microglial activation. Both potassium channel blockers, when applied on the hippocampal slices without K+, caused significantly increased microglial activation as compared to the control slices. In order to check whether the functional alteration of the neuronal population induced by 4-aminopyridine caused the activation of the microglial cells, Schaffer collaterals were cut to block spreading of epileptiform hyperactivity of the CA3 pyramidal cells to the CA1 region. No significant differences were found in microglial activation between the CA3 and CA1 regions, indicating that the effect of 4-aminopyridine on microglial cells is independent of the epileptiform activity caused by the drug.
Keywords
Glial cells epileptiform activity electrophysiology OX-42Notes
Acknowledgement
This work was supported by the grants of the Hungarian Science Research Fund (OTKA) T 025759 and A 234.
References
- 1.Ábrahám, H., Losonczy, A., Czéh, G., Lázár, Gy. (2001) Rapid activation of microglial cells by hypoxia, kainic acid, and potassium ions in slice preparations of the rat hippocampus. Brain Res. 906, 115–126.CrossRefGoogle Scholar
- 2.Bordey, A., Sontheimer, H. (2000) Ion channel expression by astrocytes in situ: comparison of different CNS region. Glia 30, 27–38.CrossRefGoogle Scholar
- 3.Boucsein, C., Kettenmann, H., Nolte, C. (2000) Electrophysiological properties of microglial cells in normal and pathological rat brain slices. Eur. J. Neurosci. 12, 2049–2058.CrossRefGoogle Scholar
- 4.Eder, C. (1998) Ion channels in microglia (brain macrophages). Am. J. Physiol. 275 (Cell Physiol. 44), C327-C342.Google Scholar
- 5.Finsen, B. R., Jorgensen, M. B., Diemer, N. H., Zimmer, J. (1993) Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus. Glia 7, 41–49.CrossRefGoogle Scholar
- 6.Gehrmann, J., Bonnekoh, P., Miyazawa, T., Hossmann, K. A., Kreutzberg, G. W. (1992) Immuno-cytochemical study of an early microglial activation in ischemia. J. Cereb. Blood Flow Metab. 12, 257–269.CrossRefGoogle Scholar
- 7.Gehrmann, J., Kreutzberg, G. W. (1995) Microglia in experimental neuropathology. In: Kettenmann, H., Ransom, B. R. (eds) Neuroglia. Oxford University Press, Oxford, pp. 883–904.Google Scholar
- 8.Hansen, A. J., Zeuthen, T. (1981) Extracellular ion concentrations during spreading depression and ischemia in the rat brain cortex. Acta Physiol. (Scand.) 113, 437–445.CrossRefGoogle Scholar
- 9.Hu, P. S., Benishin, C., Fredholm, B. B. (1991) Comparison of the effects of four dendrotoxin pep-tides, 4-aminopyridine and tetraethylammonium on the electrically evoked [3H]-noradrenaline from rat hippocampus. Eur. J. Pharmacol. 20, 87–93.CrossRefGoogle Scholar
- 10.Hu, P. S., Fredholm, B. B. (1991) 4-aminopyridine-induced increase in basal and stimulation evoked [3H]-NA release in slices from rat hippocampus: Ca2+ sensitivity and presynaptic control. Br. J. Pharmacol. 102, 764–768.CrossRefGoogle Scholar
- 11.Jou, I., Pyo, H., Chung, S., Jung, S. Y., Gwag, B. J., Joe, E. H. (1998) Expression of Kv1.5 K+ channels in activated microglia in vivo. Glia 24, 408–414.CrossRefGoogle Scholar
- 12.Kloss, C. U., Kreutzberg, G. W., Raivich, G. (1997) Proliferation of ramified microglia on an astro-cyte monolayer: characterization of stimulatory and inhibitory cytokines. J. Neurosci. Res. 49, 248–254.CrossRefGoogle Scholar
- 13.Kotecha, S. A., Schlichter, L. G. (1999) A Kv1.5 to Kv1.3 switch in endogenous hippocampal microglia and a role in proliferation. J. Neurosci. 19, 10680–10693.CrossRefGoogle Scholar
- 14.Morioka, T., Kalehua, A. H., Streit, W. J. (1991) The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia. J. Cereb. Blood Flow Metab. 11, 966–973.CrossRefGoogle Scholar
- 15.Poopalasundaram, S., Knott, C., Shamotienko, O. G., Foran, P. G., Dolly, J. O., Ghiani, C. A., Gallo, V., Wilkin, G. P. (2000) Glial heterogeneity in expression of the inwardly rectifying K(+) channel Kir4.1, in adult rat CNS. Glia 30, 362–372.CrossRefGoogle Scholar
- 16.Schechter, L. E. (1997) The potassium channel blockers 4-aminopyridine and tetraethylammonium increase the spontaneous basal release of [3H]5-hydroxytryptamine in rat hippocampal slices. J. Pharmacol. Exp. Ther. 282, 262–270.PubMedGoogle Scholar
- 17.Shaw, J. A., Perry, V. H., Mellanby, J. (1990) Tetanus toxin-induced seizures cause microglial activation in rat hippocampus. Neurosci. Lett. 120, 66–69.CrossRefGoogle Scholar
- 18.Siesjö, B. K. (1981) Cell damage in the brain. A speculative synthesis. J. Cereb. Blood Flow Metab. 1, 155–185.CrossRefGoogle Scholar
- 19.Streit, W. J., Graeber, M. B., Kreutzberg, G. W. (1988) Functional plasticity of microglia. A review. Glia 1, 301–307.CrossRefGoogle Scholar
- 20.Streit, W. J. (1995) Microglial cells. In: Kettenmann, H., Ransom, B. R. (eds) Neuroglia. Oxford University Press, Oxford, pp. 85–96.Google Scholar
- 21.Tapia, R., Sitges, M. (1982) Effect of 4-aminopyridine on transmitter release in synaptosomes. Brain Res. 250, 291–299.CrossRefGoogle Scholar
- 22.Tapia, R., Sitges, M., Morales, E. (1985) Mechanism of the calcium dependent stimulation of transmitter release by 4-aminopyridine in synaptosomes. Brain Res. 361, 373–382.CrossRefGoogle Scholar
- 23.Voskuyl, R. A., Albus, H. (1985) Spontaneous epileptiform discharges in hippocampal slices induced by 4-aminopyridine. Brain Res. 342, 54–66.CrossRefGoogle Scholar
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