Cytokines are released during acute and chronic inflammatory diseases of the CNS and activate receptors on glial cells, thereby inducing various effects such as proliferation, expression of major histocompatibility complex genes or secretion of growth factors. Here, we summarize current evidence indicating that K+ currents, Ca 2+ currents, and the activity of ion transporters on astrocytes, microglial cells, and oligodendrocytes are also affected by cytokines. In disease states with associated elevated cytokine titers, such alterations in electrophysiological properties of glial cells might contribute to the patho genesis of neurological symptoms. NEUROSCIENTIST 5:142-146, 1999
Arditi M., Manogue KR, Caplan M., Yogev R.Cerebrospinal fluid cachectin/ tumor necrosis factor α and platelet-activating factor concentrations and severity of bacterial meningitis in children. J Infect Dis1990;162:139-47.
Moreau T., Coles A., Wing M., Isaacs J., Hale G., Waldmann H., et al.Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain1996;119:225-37.
Rothwell NJ, Hopkins SJCytokines and the nervous system II: actions and mechanisms of action . Trends Neurosci1995; 18:130-6.
6.
Vincent A., Roberts M., Willison H., Lang B., Newsom-Davis J.Autoantibodies, neurotoxins and the nervous system. J Physiol1995;89:129-36.
7.
Köller H., Siebler M., Hartung HPImmunologically induced electrophysiological dysfunction - Implications for inflammatory diseases of the CNS and PNS. Prog Neurobiol1997;52:1-26.
8.
Köller H.TNFα in cerebrospinal fluid of meningitis patients reduces astrocytes membrane potential. J Neuroimmunol1997;76:185-8.
9.
Köller H., Allert N., Oel D., Stoll G., Siebler M.TNFα induces a protein kinase C dependent reduction of astroglial K+ conductance . Neuroreport1998;9:1375-8.
10.
Ilschner S. , Ohlemeyer C., Gimpl G., Kettenmann H Modulation of potassium currents in cultured murine microglial cells by receptor activation and intracellular pathways. Neuroscience1995 ;66: 983-1000.
11.
Soliven B., Szuchet S., Nelson DJTumor necrosis factor inhibits K+ current expression in cultured oligodendrocytes . J Membr Biol1991;124:127-37.
12.
McLarnon JG , Michikawa M., Kim SUEffects of tumor necrosis factor on inward potassium current and cell morphology in cultured human oligodendrocytes . Glia1993;9:120-6.
13.
Nörenberg W. , Gebicke-Haerter PJ, Illes P.Inflammatory stimuli induce a new K+ outward current in cultured rat microglia. Neurosci Lett1992;147:171-4.
14.
Visentin S. , Agresti C., Patnzio M., Levi G.Ion channels in rat microglia and their different sensitivity to lipopolysacchande and interferon γ. J Neurosci Res1995;42: 439-51.
15.
Fischer HG, Eder C., Hadding U., Heinemann U.Cytokine-dependent K+ channel profile of microglia at immunologically defined functional states. Neuroscience1995 ;64:183-91.
16.
McLarnon JG , Xu R., Lee YB, Kim SUIon channels of human microglia in culture . Neuroscience1997;78:1217-28.
Eder C., Fischer HG, Hadding U., Heinemann U.Properties of voltage-gated currents of microglia developed using macrophage colony-stimulating factor. Pflugers Arch1995 ;430:526-33.
19.
Eder C., Fischer HG, Haddmg U., Heinemann U.Properties of voltage-gated potassium currents of microglia differentiated with granulocyte/macrophage colony-stimulating factor. J Membr Biol1995;147:137-46.
20.
Köller H., Thiem K., Siebler M.Tumor necrosis factor-α increases intracellular Ca2+ and induces a depolarization in cultured astroglial cells. Brain1996; 119:2021-7.
21.
Holliday J. , Gruol DLCytokine stimulation increases intracellular calcium and alters the response to quisqualate in cultured cortical astrocytes . Brain Res1993;621:233-41.
22.
Benveniste EN , Vidovic M., Panek RB, Norris JG, Reddy AT, Benos DJInterferon-γ-induced astrocyte class II major histocompatibility complex gene expression is associated with both protein kinase C activation and Na+ entry. J Biol Chem1991;266:18119-26.
23.
Benos DJ, McPherson S., Hahn BH, Chaikin MA, Benveniste ENCytokines and HIV envelope glycoprotein gp120 stimulate Na+/H+ exchange in astrocytes. J Biol Chem1994;269:13811-16.
24.
Epstein LG, Gendelman HEHuman immunodeficiency virus type 1 infection of the nervous system: pathogenic mechanisms. Ann Neurol1993;33:429-36.
25.
Bubien JK, Benvemste EN, Benos DJHIV-gp120 activates large-conductance apamin-sensitive potassium channels in rat astrocytes. Am J Physiol1995;268: C1440-9.
26.
Codazzi F., Menegon A., Zacchetti D., Ciardo A., Grohovaz F., Meldolesi J.HIV-1 gp120 glycoprotein induces [Ca2+], responses not only in type-2 but also in type-1 astrocytes and oligodendrocytes of the rat cerebellum. Eur J Neurosci1995; 7:1333-41.
27.
Barres BA, Chun Lly, Corey DPIon channels in vertebrate glia. Annu Rev Neurosci1990;13:441-74.
28.
Ransom CB, Sontheimer H.Biophysical and pharmacological characterization of inwardly rectifying K+ currents in rat spinal cord astrocytes. J Neurophysiol1995; 73:333-46.
29.
Bordey A., Sontheimer H.Postnatal development of ionic currents in rat hippocampal astrocytes in situ . J Neurophysiol1997;78:461-77.
30.
MacFarlane SN, Sontheimer H.Electrophysiological changes that accompany reactive gliosis in vitro. J Neurosci1997 ;17: 7316-29.
31.
Francke M., Pannicke T., Biedermann B., Faude F., Wiedemann P., Reichenbach A., et al. Loss of inwardly rectifying potassium currents by human retinal glial cells in diseases of the eye. Glia1997 ;20:210-8.
32.
O'Connor ER , Sontheimer H., Spencer DD, de Lanerolle NCAstrocytes from human hippocampal epileptogenic foci exhibit action potential-like responses . Epilepsia1998;39:347-54.
33.
Fine SM, Angel RA, Perry SW, Epstein LG, Rothstem JD, Dewhurst S., et al. Tumor necrosis factor α inhibits glutamate uptake by primary human astrocytes. J Biol Chem1996;271:15303-6.
34.
Ye ZC, Sontheimer H.Cytokine modulation of glial glutamate uptake: a possible involvement of nitric oxide. Neuroreport1996;7:2181-5.
35.
Flott B., Seifert W.Characterization of glutamate uptake systems in astrocyte pnmary cultures from rat brain. Glia1991; 4:293-304.
36.
Janigro D., Gaspanni S., D'Ambrosio R., McKhann G., DiFrancesco D.Reduction of K+ uptake in glia prevents long-term depression maintenance and causes epileptiform activity. J Neurosci1997 ;17: 2813-24.
Mattson MP, Cheng B., Baldwin SA, Smith-Swintosky VL, Keller J., Geddes JW, et al. Brain injury and tumor necrosis factors induce calbindin D-28k in astrocytes : Evidence for a cytoprotective response. J Neurosci Res1995;42:357-70.
39.
Vyas S., Michel, PP, Copin MC, Biguet NF, Thomasset M., Agid Y.Induction of calbindin-D 28K gene and protein expression by physiological stimuli but not in calcium-mediated degeneration in rat PC12 pheochromocytoma cells. FEBS Lett1994;351:53-7.
40.
Neumann H., Boucraut J., Hahnel C., Misgeld T., Wekerle H.Neuronal control of MHC class II inducibility in rat astrocytes and microglia . Eur J Neurosci1996;8:2582-90.
