Activation of KCNN3/SK3/K(Ca)2. 3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia(557 views) Dolga AM, Letsche T, Gold M, Doti N, Bacher M, Chiamvimonvat N, Dodel R, Culmsee C
Institute of Pharmacology and Clinical Pharmacy, Philipps University of Marburg, 35032, Marburg, Germany. dolga@staff.uni-marburg.de
Department of Neurology, Philipps University of Marburg, 35043, Marburg, Germany
Institute of Biostructures and Bioimaging-CNR, 16-80131, Naples, Italy
Department of Medicine, University of California, Davis, CA, United States
References: Allen, D., Nakayama, S., Kuroiwa, M., Nakano, T., Palmateer, J., Kosaka, Y., Ballesteros, C., Herson, P.S., SK2 channels are neuroprotective for ischemia-induced neuronal cell death (2011) J Cereb Blood Flow Metab, 31, pp. 2302-231
Beck, A., Penner, R., Fleig, A., Lipopolysaccharide-induced down-regulation of Ca2+ release-activated Ca2+ currents (I CRAC) but not Ca2+-activated TRPM4-like currents (I CAN) in cultured mouse microglial cells (2008) J Physiol, 586, pp. 427-439
Bordey, A., Spencer, D.D., Chemokine modulation of high-conductance Ca2+-sensitive K+ currents in microglia from human hippocampi (2003) Eur J Neurosci, 18, pp. 2893-2898
Boucsein, C., Kettenmann, H., Nolte, C., Electrophysiological properties of microglial cells in normal and pathologic rat brain slices (2000) Eur J Neurosci, 12, pp. 2049-2058
Chan, W.Y., Kohsaka, S., Rezaie, P., The origin and cell lineage of microglia-New concepts (2007) Brain Res Rev, 53, pp. 344-354
Choi, H.B., Ryu, J.K., Kim, S.U., McLarnon, J.G., Modulation of the purinergic P2X7 receptor attenuates lipopolysaccharide-mediated microglial activation and neuronal damage in inflamed brain (2007) J Neurosci, 27, pp. 4957-4968
Diemert, S., Dolga, A.M., Tobaben, S., Grohm, J., Pfeifer, S., Oexler, E., Culmsee, C., Impedance measurement for real time detection of neuronal cell death (2012) J Neurosci Methods, 203, pp. 69-77
Dolga, A.M., Granic, I., Blank, T., Knaus, H.G., Spiess, J., Luiten, P.G., Eisel, U.L., Nijholt, I.M., TNF-alpha mediates neuroprotection against glutamate-induced excitotoxicity via NF-kappaB-dependent up-regulation of KCa2 channels (2008) J Neurochem, 107, pp. 1158-1167
Dolga, A.M., Terpolilli, N., Kepura, F., Nijholt, I.M., Knaus, H.G., D'Orsi, B., Prehn, J.H., Culmsee, C., KCa2 channels activation prevents [Ca2+]i deregulation and reduces neuronal death following glutamate toxicity and cerebral ischemia (2011) Cell Death Dis, 2, pp. e147
Farkas, E., Annaházi, A., Institóris, A., Mihály, A., Luiten, P.G., Bari, F., Diazoxide and dimethyl sulphoxide alleviate experimental cerebral hypoperfusion-induced white matter injury in the rat brain (2005) Neurosci Lett, 373, pp. 195-199
Goghari, V., Franciosi, S., Kim, S.U., Lee, Y.B., McLarnon, J.G., Acute application of interleukin-1beta induces Ca2+ responses in human microglia (2000) Neurosci Lett, 281, pp. 83-86
Hanisch, U.K., Prinz, M., Angstwurm, K., Häusler, K.G., Kann, O., Kettenmann, H., Weber, J.R., The protein tyrosine kinase inhibitor AG126 prevents the massive microglial cytokine induction by pneumococcal cell walls (2001) Eur J Immunol, 31, pp. 2104-2115
Hoffmann, A., Kann, O., Ohlemeyer, C., Hanisch, U.K., Kettenmann, H., Elevation of basal intracellular calcium as a central element in the activation of brain macrophages (microglia): Suppression of receptor-evoked calcium signaling and control of release function (2003) J Neurosci, 23, pp. 4410-4419
Hougaard, C., Eriksen, B.L., Jørgensen, S., Johansen, T.H., Dyhring, T., Madsen, L.S., Strøbaek, D., Christophersen, P., Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+-activated K+ channels (2007) Br J Pharmacol, 151, pp. 655-665
Jelassi, B., Chantôme, A., Alcaraz-Pérez, F., Baroja-Mazo, A., Cayuela, M.L., Pelegrin, P., Surprenant, A., Roger, S., P2X(7) receptor activation enhances SK3 channels- and cystein cathepsin-dependent cancer cells invasiveness (2011) Oncogene, 30, pp. 2108-2122
Kaushal, V., Koeberle, P.D., Wang, Y., Schlichter, L.C., The Ca2+-activated K+ channel KCNN4/KCa3.1 contributes to microglia activation and nitric oxide-dependent neurodegeneration (2007) J Neurosci, 27, pp. 234-244
Keller, C., Hellsten, Y., Steensberg, A., Pedersen, B.K., Differential regulation of IL-6 and TNF-alpha via calcineurin in human skeletal muscle cells (2006) Cytokine, 36, pp. 141-147
Kettenmann, H., Hanisch, U.K., Noda, M., Verkhratsky, A., Physiology of microglia (2011) Physiol Rev, 91, pp. 461-553
Kettenmann, H., Hoppe, D., Gottmann, K., Banati, R., Kreutzberg, G., Cultured microglial cells have a distinct pattern of membrane channels different from peritoneal macrophages (1990) J Neurosci Res, 26, pp. 278-287
Khanna, R., Roy, L., Zhu, X., Schlichter, L.C., K+ channels and the microglial respiratory burst (2001) Am J Physiol Cell Physiol, 280, pp. C796-C806
Koistinaho, M., Koistinaho, J., Role of p38 and p44/42 Mitogen-activated protein kinases in microglia (2002) Glia, 40, pp. 175-183
Launay, P., Cheng, H., Srivatsan, S., Penner, R., Fleig, A., Kinet, J.P., TRPM4 regulates calcium oscillations after T cell activation (2004) Science, 306, pp. 1374-1377
Liu, B.S., Ferreira, R., Lively, S., Schlichter, L.C., Microglial SK3 and SK4 currents and activation state are modulated by the neuroprotective drug, Riluzole (2012) J Neuroimmune Pharmacol, , Epub ahead of print]
Liva, S.M., Kahn, M.A., Dopp, J.M., de Vellis, J., Signal transduction pathways induced by GM-CSF in microglia: Significance in the control of proliferation (1999) Glia, 26, pp. 344-352
Marriott, I., Bost, K.L., Mason, M.J., Differential kinetics for induction of interleukin-6 mRNA expression in murine peritoneal macrophages: Evidence for calcium-dependent and independent-signalling pathways (1998) J Cell Physiol, 177, pp. 232-240
Möller, T., Calcium signaling in microglial cells (2002) Glia, 40, pp. 184-194
Pedarzani, P., D'hoedt, D., Doorty, K.B., Wadsworth, J.D., Joseph, J.S., Jeyaseelan, K., Kini, R.M., Strong, P.N., Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+-activated K+ channels and afterhyperpolarization currents in central neurons (2002) J Biol Chem, 277, pp. 46101-46109
Pedarzani, P., Stocker, M., Molecular and cellular basis of small- and intermediate-conductance, calcium-activated potassium channel function in the brain (2008) Cell Mol Life Sci, 65, pp. 3196-3217
Rupalla, K., Allegrini, P.R., Sauer, D., Wiessner, C., Time course of microglia activation and apoptosis in various brain regions after permanent focal cerebral ischemia in mice (1998) Acta Neuropathol, 96, pp. 172-178
Sailer, C.A., Kaufmann, W.A., Marksteiner, J., Knaus, H.G., Comparative immunohistochemical distribution of three small-conductance Ca2+-activated potassium channel subunits, SK1, SK2, and SK3 in mouse brain (2004) Mol Cell Neurosci, 26, pp. 458-469
Saura, J., Tusell, J.M., Serratosa, J., High-yield isolation of murine microglia by mild trypsinization (2003) Glia, 44, pp. 183-189
Schlichter, L.C., Kaushal, V., Moxon-Emre, I., Sivagnanam, V., Vincent, C., The Ca2+ activated SK3 channel is expressed in microglia in the rat striatum and contributes to microglia-mediated neurotoxicity in vitro (2010) J Neuroinflammation, 7, pp. -4
Skaper, S.D., Ion channels on microglia: Therapeutic targets for neuroprotection (2011) CNS Neurol Disord Drug Targets, 10, pp. 44-56
Stocker, M., Ca2+-activated K+ channels: Molecular determinants and function of the SK family (2004) Nat Rev Neurosci, 10, pp. 758-770
Tuteja, D., Rafizadeh, S., Timofeyev, V., Wang, S., Zhang, Z., Li, N., Mateo, R.K., Chiamvimonvat, N., Cardiac small conductance Ca2+-activated K+ channel subunits form heteromultimers via the coiled-coil domains in the C termini of the channels (2010) Circ Res, 107, pp. 851-859
Wulff, H., Miller, M.J., Hansel, W., Grissmer, S., Cahalan, M.D., Chandy, K.G., Design of a potent and selective inhibitor of the intermediate-conductance Ca2+-activated K+ channel, IKCa1: A potential immunosuppressant (2000) Proc Natl Acad Sci USA, 97, pp. 8151-8156
Chan, W. Y., Kohsaka, S., Rezaie, P., The origin and cell lineage of microglia-New concepts (2007) Brain Res Rev, 53, pp. 344-354
Choi, H. B., Ryu, J. K., Kim, S. U., McLarnon, J. G., Modulation of the purinergic P2X7 receptor attenuates lipopolysaccharide-mediated microglial activation and neuronal damage in inflamed brain (2007) J Neurosci, 27, pp. 4957-4968
Dolga, A. M., Granic, I., Blank, T., Knaus, H. G., Spiess, J., Luiten, P. G., Eisel, U. L., Nijholt, I. M., TNF-alpha mediates neuroprotection against glutamate-induced excitotoxicity via NF-kappaB-dependent up-regulation of KCa2 channels (2008) J Neurochem, 107, pp. 1158-1167
Dolga, A. M., Terpolilli, N., Kepura, F., Nijholt, I. M., Knaus, H. G., D'Orsi, B., Prehn, J. H., Culmsee, C., KCa2 channels activation prevents [Ca2+] i deregulation and reduces neuronal death following glutamate toxicity and cerebral ischemia (2011) Cell Death Dis, 2, pp. e147
Farkas, E., Annah zi, A., Instit ris, A., Mih ly, A., Luiten, P. G., Bari, F., Diazoxide and dimethyl sulphoxide alleviate experimental cerebral hypoperfusion-induced white matter injury in the rat brain (2005) Neurosci Lett, 373, pp. 195-199
Hanisch, U. K., Prinz, M., Angstwurm, K., H usler, K. G., Kann, O., Kettenmann, H., Weber, J. R., The protein tyrosine kinase inhibitor AG126 prevents the massive microglial cytokine induction by pneumococcal cell walls (2001) Eur J Immunol, 31, pp. 2104-2115
Jelassi, B., Chant me, A., Alcaraz-P rez, F., Baroja-Mazo, A., Cayuela, M. L., Pelegrin, P., Surprenant, A., Roger, S., P2X (7) receptor activation enhances SK3 channels- and cystein cathepsin-dependent cancer cells invasiveness (2011) Oncogene, 30, pp. 2108-2122
Liu, B. S., Ferreira, R., Lively, S., Schlichter, L. C., Microglial SK3 and SK4 currents and activation state are modulated by the neuroprotective drug, Riluzole (2012) J Neuroimmune Pharmacol, , Epub ahead of print]
Liva, S. M., Kahn, M. A., Dopp, J. M., de Vellis, J., Signal transduction pathways induced by GM-CSF in microglia: Significance in the control of proliferation (1999) Glia, 26, pp. 344-352
M ller, T., Calcium signaling in microglial cells (2002) Glia, 40, pp. 184-194
Sailer, C. A., Kaufmann, W. A., Marksteiner, J., Knaus, H. G., Comparative immunohistochemical distribution of three small-conductance Ca2+-activated potassium channel subunits, SK1, SK2, and SK3 in mouse brain (2004) Mol Cell Neurosci, 26, pp. 458-469
Skaper, S. D., Ion channels on microglia: Therapeutic targets for neuroprotection (2011) CNS Neurol Disord Drug Targets, 10, pp. 44-56
Activation of KCNN3/SK3/K(Ca)2. 3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia
In neurons, small-conductance calcium-activated potassium (KCNN/SK/KCa2) channels maintain calcium homeostasis after N-methyl-D-aspartate (NMDA) receptor activation, thereby preventing excitotoxic neuronal death. So far, little is known about the function of KCNN/SK/KCa2 channels in non-neuronal cells, such as microglial cells. In this study, we addressed the question whether KCNN/SK/KCa2 channels activation affected inflammatory responses of primary mouse microglial cells upon lipopolysaccharide (LPS) stimulation. We found that N-cyclohexyl-N- [2- (3, 5-dimethyl-pyrazol-1-yl) -6-methyl-4-pyrimidinamine (CyPPA), a positive pharmacological activator of KCNN/SK/KCa2 channels, significantly reduced LPS-stimulated activation of microglia in a concentration-dependent manner. The general KCNN/SK/KCa2 channel blocker apamin reverted these effects of CyPPA on microglial proliferation. Since calcium plays a central role in microglial activation, we further addressed whether KCNN/SK/KCa2 channel activation affected the changes of intracellular calcium levels, [Ca2+] i,, in microglial cells. Our data show that LPS-induced elevation of [Ca2+] i was attenuated following activation of KCNN2/3/KCa2. 2/KCa2. 3 channels by CyPPA. Furthermore, CyPPA reduced downstream events including tumor necrosis factor alpha and interleukin 6 cytokine production and nitric oxide release in activated microglia. Further, we applied specific peptide inhibitors of the KCNN/SK/KCa2 channel subtypes to identify which particular channel subtype mediated the observed anti-inflammatory effects. Only inhibitory peptides targeting KCNN3/SK3/KCa2. 3 channels, but not KCNN2/SK2/KCa2. 2 channel inhibition, reversed the CyPPA-effects on LPS-induced microglial proliferation. These findings revealed that KCNN3/SK3/KCa2. 3 channels can modulate the LPS-induced inflammatory responses in microglial cells. Thus, KCNN3/SK3/KCa2. 3 channels may serve as a therapeutic target for reducing microglial activity and related inflammatory responses in the central nervous system. 2012 Wiley Periodicals, Inc
Activation of KCNN3/SK3/K(Ca)2. 3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia
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Activation of KCNN3/SK3/K(Ca)2. 3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia