Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction(520 views) Dolga AM, Netter MF, Perocchi F, Doti N, Meissner L, Tobaben S, Grohm J, Zischka H, Plesnila N, Decher N, Culmsee C
Institut fur Pharmakologie und Klinische Pharmazie, Fachbereich Pharmazie, Philipps-Universitat Marburg, D-35032 Marburg, Germany. dolga@staff.uni-marburg.de
Institut für Pharmakologie und Klinische Pharmazie, Fachbereich Pharmazie, Philipps-Universität Marburg, D-35032 Marburg, Germany
Institut für Physiologie und Pathophysiologie, Vegetative Physiologie, Fachbereich Medizin, D-35037 Marburg, Germany
Department of Systems Biology and Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, United States
Gene Center, Ludwig Maximilians University, Feodor-Lynen Strasse 25, 81377 Munich, Germany
Department of Neurodegeneration, Royal College of Surgeons in Ireland, Dublin 2, Ireland
Institute of Biostructures and Bioimaging, National Research Council (CNR), 16-80131 Naples, Italy
Institute of Stroke and Dementia Research, University of Munich Medical School, D-81377 Munich, Germany
Institute of Toxicology, Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH), D-85764 Neuherberg, Germany
Institut f r Pharmakologie und Klinische Pharmazie, Fachbereich Pharmazie, Philipps-Universit t Marburg, D-35032 Marburg, Germany
Institut f r Physiologie und Pathophysiologie, Vegetative Physiologie, Fachbereich Medizin, D-35037 Marburg, Germany
References: Jentsch, T.J., Neuronal KCNQ potassium channels: Physiology and role in disease (2000) Nat. Rev. Neurosci, 1, pp. 21-3
Liu, D., Pitta, M., Lee, J.H., Ray, B., Lahiri, D.K., Furukawa, K., Mughal, M., Mattson, M.P., The KATP channel activator diazoxide ameliorates amyloid-γ and tau pathologies and improves memory in the 3xTgAD mouse model of Alzheimer's disease (2010) J. Alzheimers Dis, 22, pp. 443-457
Wang, Y., Yang, P.L., Tang, J.F., Lin, J.F., Cai, X.H., Wang, X.T., Zheng, G.Q., Potassium channels: Possible new therapeutic targets in Parkinson's disease (2008) Med. Hypotheses, 71, pp. 546-550
Poulopoulou, C., Markakis, I., Davaki, P., Tsaltas, E., Rombos, A., Hatzimanolis, A., Vassilopoulos, D., Aberrant modulation of a delayed rectifier potassium channel by glutamate in Alzheimer's disease (2010) Neurobiol. Dis, 37, pp. 339-348
Ngo-Anh, T.J., Bloodgood, B.L., Lin, M., Sabatini, B.L., Maylie, J., Adelman, J.P., SK channels and NMDA receptors form a Ca2+- mediated feedback loop in dendritic spines (2005) Nat. Neurosci, 8, pp. 642-649
Faber, E.S., Delaney, A.J., Sah, P., SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala (2005) Nat. Neurosci, 8, pp. 635-641
Stocker, M., Ca2+-activated K2+ channels: Molecular determinants and function of the SK family (2004) Nat. Rev. Neurosci, 5, pp. 758-770
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
Dolga, A.M., Granic, I., Blank, T., Knaus, H.G., Spiess, J., Luiten, P.G., Eisel, U.L., Nijholt, I.M., TNF-γ-mediates neuroprotection against glutamate-induced excitotoxicity via NF-γB-dependent up-regulation of K2.2 channels (2008) J. Neurochem, 107, pp. 1158-1167
Bednarczyk, P., Potassium channels in brain mitochondria (2009) Acta Biochim. Pol, 56, pp. 385-392
Szewczyk, A., Kajma, A., Malinska, D., Wrzosek, A., Bednarczyk, P., Zabłocka, B., Dołowy, K., Pharmacology of mitochondrial potassium channels: Dark side of the field (2010) FEBS Lett, 584, pp. 2063-2069
Szabo, I., Bock, J., Jekle, A., Soddemann, M., Adams, C., Lang, F., Zoratti, M., Gulbins, E., A novel potassium channel in lymphocyte mitochondria (2005) J. Biol. Chem, 280, pp. 12790-12798
Szabo, I., Zoratti, M., Gulbins, E., Contribution of voltage-gated potassium channels to the regulation of apoptosis (2010) FEBS Lett, 584, pp. 2049-2056
Peixoto, P.M., Ryu, S.Y., Kinnally, K.W., Mitochondrial ion channels as therapeutic targets (2010) FEBS Lett, 584, pp. 2142-2152
Malinska, D., Mirandola, S.R., Kunz, W.S., Mitochondrial potassium channels and reactive oxygen species (2010) FEBS Lett, 584, pp. 2043-2048
Cheng, Y., Debska-Vielhaber, G., Siemen, D., Interaction of mitochondrial potassium channels with the permeability transition pore (2010) FEBS Lett, 584, pp. 2005-2012
Grohm, J., Kim, S.W., Mamrak, U., Tobaben, S., Cassidy-Stone, A., Nunnari, J., Plesnila, N., Culmsee, C., Inhibition of Drp1 provides neuroprotection in vitro and in vivo (2012) Cell Death Differ, 19, pp. 1446-1458
Tobaben, S., Grohm, J., Seiler, A., Conrad, M., Plesnila, N., Culmsee, C., Bid-mediated mitochondrial damage is a key mechanism in glutamate- induced oxidative stress and AIF-dependent cell death in immortalized HT-22 hippocampal neurons (2011) Cell Death Differ, 18, pp. 282-292
Landshamer, S., Hoehn, M., Barth, N., Duvezin-Caubet, S., Schwake, G., Tobaben, S., Kazhdan, I., Culmsee, C., Bidinduced release of AIF from mitochondria causes immediate neuronal cell death (2008) Cell Death Differ, 15, pp. 1553-15563
Culmsee, C., Zhu, C., Landshamer, S., Becattini, B., Wagner, E., Pellecchia, M., Blomgren, K., Plesnila, N., Apoptosis-inducing factor triggered by poly(ADP-ribose) polymerase and Bid mediates neuronal cell death after oxygen-glucose deprivation and focal cerebral ischemia (2005) J. Neurosci, 25, pp. 10262-10272
Oxler, E.M., Dolga, A., Culmsee, C., AIF depletion provides neuroprotection through a preconditioning effect (2012) Apoptosis, 17, pp. 1027-1038
Sorgato, M.C., Keller, B.U., Stuhmer, W., Patch-clamping of the inner mitochondrial membrane reveals a voltage-dependent ion channel (1987) Nature, 330, pp. 498-500
Hochman, J., Ferguson-Miller, S., Schindler, M., Mobility in the mitochondrial electron transport chain (1985) Biochemistry, 24, pp. 2509-2516
Kirichok, Y., Krapivinsky, G., Clapham, D.E., The mitochondrial calcium uniporter is a highly selective ion channel (2004) Nature, 427, pp. 360-364
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
Mootha, V.K., Lepage, P., Miller, K., Bunkenborg, J., Reich, M., Hjerrild, M., Delmonte, T., Lander, E.S., Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics (2003) Proc. Natl. Acad. Sci. U.S.A, 100, pp. 605-610
Baughman, J.M., Perocchi, F., Girgis, H.S., Plovanich, M., Belcher- Timme, C.A., Sancak, Y., Bao, X.R., Mootha, V.K., Integrative genomics identifiesMCUas an essential component of the mitochondrial calcium uniporter (2011) Nature, 476, pp. 341-345
Blank, T., Nijholt, I., Kye, M.J., Radulovic, J., Spiess, J., Smallconductance, Ca2+-activated K2+ channel SK3 generates age-related memory and LTP deficits (2003) Nat. Neurosci, 6, pp. 911-912
Tuteja, D., Rafizadeh, S., Timofeyev, V., Wang, S., Zhang, Z., Li, N., Mateo, R.K., Chiamvimonvat, N., Cardiac small conductance Ca2+-activated K2+ channel subunits form heteromultimers via the coiled-coil domains in the C termini of the channels (2010) Circ. Res, 107, pp. 851-859
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
Emanuelsson, O., Nielsen, H., Brunak, S., Von Heijne, G., Predicting subcellular localization of proteins based on their N-terminal amino acid sequence (2000) J. Mol. Biol, 300, pp. 1005-1016
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 K2+ channels (2007) Br. J. Pharmacol, 151, pp. 655-665
Strøbaek, D., Hougaard, C., Johansen, T.H., Sørensen, U.S., Nielsen, K.S., Taylor, R.D., Pedarzani, P., Christophersen, P., Inhibitory gating modulation of small conductance Ca2+- activated K2+ channels by the synthetic compound (R)-N-(benzimidazol- 2-yl)-1,2,3,4- tetrahydro-1-naphtylamine (NS8593) reduces afterhyperpolarizing current in hippocampal CA1 neurons (2006) Mol. Pharmacol, 70, pp. 1771-1782
Ishii, T.M., Maylie, J., Adelman, J.P., Determinants of apamin and d-tubocurarine block in SK potassium channels (1997) J. Biol. Chem, 272, pp. 23195-23200
Adelman, J.P., Maylie, J., Sah, P., Small-conductance Ca2+- activated K+ channels: Form and function (2012) Annu. Rev. Physiol, 74, pp. 245-269
Hirschberg, B., Maylie, J., Adelman, J.P., Marrion, N.V., Gating of recombinant small-conductance Ca-activated K+ channels by calcium (1998) J. Gen. Physiol, 111, pp. 565-581
Soh, H., Park, C.S., Inwardly rectifying current-voltage relationship of small-conductance Ca2+-activated K+ channels rendered by intracellular divalent cation blockade (2001) Biophys. J, 80, pp. 2207-2215
Yarov-Yarovoy, V., Paucek, P., Jabůrek, M., Garlid, K.D., The nucleotide regulatory sites on the mitochondrial KATP channel face the cytosol (1997) Biochim. Biophys. Acta, 1321, pp. 128-136
Jabůrek, M., Yarov-Yarovoy, V., Paucek, P., Garlid, K.D., Statedependent inhibition of the mitochondrial KATP channel by glyburide and 5-hydroxydecanoate (1998) J. Biol. Chem, 273, pp. 13578-13582
Garcia, M.L., Galvez, A., Garcia-Calvo, M., King, V.F., Vazquez, J., Kaczorowski, G.J., Use of toxins to study potassium channels (1991) J. Bioenerg. Biomembr, 23, pp. 615-646
Maher, P., Davis, J.B., The role of monoamine metabolism in oxidative glutamate toxicity (1996) J. Neurosci, 16, pp. 6394-6401
Albrecht, P., Lewerenz, J., Dittmer, S., Noack, R., Maher, P., Methner, A., Mechanisms of oxidative glutamate toxicity: The glutamate/cystine antiporter system xc as a neuroprotective drug target (2010) CNS Neurol. Disord. Drug Targets, 9, pp. 373-382
Kasumu, A.W., Hougaard, C., Rode, F., Jacobsen, T.A., Sabatier, J.M., Eriksen, B.L., Strøbæk, D., Bezprozvanny, I., Selective positive modulator of calcium-activated potassium channels exerts beneficial effects in a mouse model of spinocerebellar ataxia type 2 (2012) Chem. Biol, 19, pp. 1340-1353
Walter, J.T., Alvina, K., Womack, M.D., Chevez, C., Khodakhah, K., Decreases in the precision of Purkinje cell pacemaking cause cerebellar dysfunction and ataxia (2006) Nat. Neurosci, 9, pp. 389-397
Alvina, K., Khodakhah, K., The therapeutic mode of action of 4-aminopyridine in cerebellar ataxia (2010) J. Neurosci, 30, pp. 7249-7257
Marchi, S., Giorgi, C., Suski, J.M., Agnoletto, C., Bononi, A., Bonora, M., De Marchi, E., Pinton, P., Mitochondria-ros crosstalk in the control of cell death and aging (2012) J. Signal Transduct, 2012, p. 329635
Dolga, A.M., Letsche, T., Gold, M., Doti, N., Bacher, M., Chiamvimonvat, N., Dodel, R., Culmsee, C., Activation of KCNN3/SK3/KCa2.3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia (2012) Glia, 60, pp. 2050-2064
Dolga, A.M., Culmsee, C., Protective roles for potassium SK/ KCa2 channels in microglia and neurons (2012) Front. Pharmacol, 3, p. 196
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. 2302-2312
Bishop, M.W., Chakraborty, S., Matthews, G.A., Dougalis, A., Wood, N.W., Festenstein, R., Ungless, M.A., Hyperexcitable substantia nigra dopamine neurons in PINK1- and HtrA2/Omi-deficient mice (2010) J. Neurophysiol, 104, pp. 3009-3020
Eliseev, R.A., Salter, J.D., Gunter, K.K., Gunter, T.E., Bcl-2 and tBid proteins counter-regulate mitochondrial potassium transport (2003) Biochim. Biophys. Acta, 1604, pp. 1-5
Jaburek, M., Yarov-Yarovoy, V., Paucek, P., Garlid, K.D., Statedependent inhibition of the mitochondrial KATP channel by glyburide and 5-hydroxydecanoate (1998) J. Biol. Chem, 273, pp. 13578-13582
Jentsch, T. J., Neuronal KCNQ potassium channels: Physiology and role in disease (2000) Nat. Rev. Neurosci, 1, pp. 21-3
Wang, Y., Yang, P. L., Tang, J. F., Lin, J. F., Cai, X. H., Wang, X. T., Zheng, G. Q., Potassium channels: Possible new therapeutic targets in Parkinson's disease (2008) Med. Hypotheses, 71, pp. 546-550
Ngo-Anh, T. J., Bloodgood, B. L., Lin, M., Sabatini, B. L., Maylie, J., Adelman, J. P., SK channels and NMDA receptors form a Ca2+- mediated feedback loop in dendritic spines (2005) Nat. Neurosci, 8, pp. 642-649
Faber, E. S., Delaney, A. J., Sah, P., SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala (2005) Nat. Neurosci, 8, pp. 635-641
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
Dolga, A. M., Granic, I., Blank, T., Knaus, H. G., Spiess, J., Luiten, P. G., Eisel, U. L., Nijholt, I. M., TNF- -mediates neuroprotection against glutamate-induced excitotoxicity via NF- B-dependent up-regulation of K2. 2 channels (2008) J. Neurochem, 107, pp. 1158-1167
Peixoto, P. M., Ryu, S. Y., Kinnally, K. W., Mitochondrial ion channels as therapeutic targets (2010) FEBS Lett, 584, pp. 2142-2152
Grohm, J., Kim, S. W., Mamrak, U., Tobaben, S., Cassidy-Stone, A., Nunnari, J., Plesnila, N., Culmsee, C., Inhibition of Drp1 provides neuroprotection in vitro and in vivo (2012) Cell Death Differ, 19, pp. 1446-1458
Oxler, E. M., Dolga, A., Culmsee, C., AIF depletion provides neuroprotection through a preconditioning effect (2012) Apoptosis, 17, pp. 1027-1038
Sorgato, M. C., Keller, B. U., Stuhmer, W., Patch-clamping of the inner mitochondrial membrane reveals a voltage-dependent ion channel (1987) Nature, 330, pp. 498-500
Mootha, V. K., Lepage, P., Miller, K., Bunkenborg, J., Reich, M., Hjerrild, M., Delmonte, T., Lander, E. S., Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics (2003) Proc. Natl. Acad. Sci. U. S. A, 100, pp. 605-610
Baughman, J. M., Perocchi, F., Girgis, H. S., Plovanich, M., Belcher- Timme, C. A., Sancak, Y., Bao, X. R., Mootha, V. K., Integrative genomics identifiesMCUas an essential component of the mitochondrial calcium uniporter (2011) Nature, 476, pp. 341-345
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
Str baek, D., Hougaard, C., Johansen, T. H., S rensen, U. S., Nielsen, K. S., Taylor, R. D., Pedarzani, P., Christophersen, P., Inhibitory gating modulation of small conductance Ca2+- activated K2+ channels by the synthetic compound (R) -N- (benzimidazol- 2-yl) -1, 2, 3, 4- tetrahydro-1-naphtylamine (NS8593) reduces afterhyperpolarizing current in hippocampal CA1 neurons (2006) Mol. Pharmacol, 70, pp. 1771-1782
Ishii, T. M., Maylie, J., Adelman, J. P., Determinants of apamin and d-tubocurarine block in SK potassium channels (1997) J. Biol. Chem, 272, pp. 23195-23200
Adelman, J. P., Maylie, J., Sah, P., Small-conductance Ca2+- activated K+ channels: Form and function (2012) Annu. Rev. Physiol, 74, pp. 245-269
Soh, H., Park, C. S., Inwardly rectifying current-voltage relationship of small-conductance Ca2+-activated K+ channels rendered by intracellular divalent cation blockade (2001) Biophys. J, 80, pp. 2207-2215
Jab rek, M., Yarov-Yarovoy, V., Paucek, P., Garlid, K. D., Statedependent inhibition of the mitochondrial KATP channel by glyburide and 5-hydroxydecanoate (1998) J. Biol. Chem, 273, pp. 13578-13582
Garcia, M. L., Galvez, A., Garcia-Calvo, M., King, V. F., Vazquez, J., Kaczorowski, G. J., Use of toxins to study potassium channels (1991) J. Bioenerg. Biomembr, 23, pp. 615-646
Kasumu, A. W., Hougaard, C., Rode, F., Jacobsen, T. A., Sabatier, J. M., Eriksen, B. L., Str b k, D., Bezprozvanny, I., Selective positive modulator of calcium-activated potassium channels exerts beneficial effects in a mouse model of spinocerebellar ataxia type 2 (2012) Chem. Biol, 19, pp. 1340-1353
Walter, J. T., Alvina, K., Womack, M. D., Chevez, C., Khodakhah, K., Decreases in the precision of Purkinje cell pacemaking cause cerebellar dysfunction and ataxia (2006) Nat. Neurosci, 9, pp. 389-397
Dolga, A. M., Letsche, T., Gold, M., Doti, N., Bacher, M., Chiamvimonvat, N., Dodel, R., Culmsee, C., Activation of KCNN3/SK3/KCa2. 3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia (2012) Glia, 60, pp. 2050-2064
Dolga, A. M., Culmsee, C., Protective roles for potassium SK/ KCa2 channels in microglia and neurons (2012) Front. Pharmacol, 3, p. 196
Bishop, M. W., Chakraborty, S., Matthews, G. A., Dougalis, A., Wood, N. W., Festenstein, R., Ungless, M. A., Hyperexcitable substantia nigra dopamine neurons in PINK1- and HtrA2/Omi-deficient mice (2010) J. Neurophysiol, 104, pp. 3009-3020
Eliseev, R. A., Salter, J. D., Gunter, K. K., Gunter, T. E., Bcl-2 and tBid proteins counter-regulate mitochondrial potassium transport (2003) Biochim. Biophys. Acta, 1604, pp. 1-5
Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction
Small conductance calcium-activated potassium (SK2/K(Ca)2.2) channels are known to be located in the neuronal plasma membrane where they provide feedback control of NMDA receptor activity. Here, we provide evidence that SK2 channels are also located in the inner mitochondrial membrane of neuronal mitochondria. Patch clamp recordings in isolated mitoplasts suggest insertion into the inner mitochondrial membrane with the C and N termini facing the intermembrane space. Activation of SK channels increased mitochondrial K+ currents, whereas channel inhibition attenuated these currents. In a model of glutamate toxicity, activation of SK2 channels attenuated the loss of the mitochondrial transmembrane potential, blocked mitochondrial fission, prevented the release of proapoptotic mitochondrial proteins, and reduced cell death. Neuroprotection was blocked by specific SK2 inhibitory peptides and siRNA targeting SK2 channels. Activation of mitochondrial SK2 channels may therefore represent promising targets for neuroprotective strategies in conditions of mitochondrial dysfunction.
Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction
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Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction