publication . Article . Other literature type . 2018

Microglial Ramification, Surveillance, and Interleukin-1β Release Are Regulated by the Two-Pore Domain K+ Channel THIK-1

Madry, Christian; Kyrargyri, Vasiliki; Arancibia-Cárcamo, I. Lorena; Jolivet, Renaud; Kohsaka, Shinichi; Bryan, Robert M.; Attwell, David;
Open Access
  • Published: 01 Jan 2018 Journal: Neuron, volume 97, pages 299-312,000,000 (issn: 0896-6273, Copyright policy)
  • Publisher: Elsevier BV
Abstract
Summary Microglia exhibit two modes of motility: they constantly extend and retract their processes to survey the brain, but they also send out targeted processes to envelop sites of tissue damage. We now show that these motility modes differ mechanistically. We identify the two-pore domain channel THIK-1 as the main K+ channel expressed in microglia in situ. THIK-1 is tonically active, and its activity is potentiated by P2Y12 receptors. Inhibiting THIK-1 function pharmacologically or by gene knockout depolarizes microglia, which decreases microglial ramification and thus reduces surveillance, whereas blocking P2Y12 receptors does not affect membrane potential, ...
Subjects
free text keywords: General Neuroscience, Biology, Cytokine, medicine.medical_treatment, medicine, Receptor, Cell biology, Potassium channel, Motility, Inflammasome, medicine.drug, Membrane potential, Gene knockout, Microglia, medicine.anatomical_structure, Article, ATP, surveillance, interleukin-1β, ramification, THIK-1
Funded by
SNSF| Phases incommensurables, structures désordonnées, diffusion diffuse
Project
  • Funder: Swiss National Science Foundation (SNSF)
  • Project Code: 2000-046666
  • Funding stream: Project funding | Project funding (Div. I-III)
,
NIH| Function of Two-Pore Domain K Channels in Vascular Smooth Muscle
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R21HL098921-02
  • Funding stream: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
,
WT| Novel aspects of neurotransmitter signalling and its regulation by transporters in health and disease.
Project
  • Funder: Wellcome Trust (WT)
  • Project Code: 075232
  • Funding stream: Neuroscience and Mental Health
,
WT| The development, plasticity and pathology of myelinated CNS axons.
Project
  • Funder: Wellcome Trust (WT)
  • Project Code: 099222
  • Funding stream: Neuroscience and Mental Health
,
NIH| EDHF in the Cerebral Circulation
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01NS046666-05
  • Funding stream: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
66 references, page 1 of 5

Bernardino, L., Balosso, S., Ravizza, T., Marchi, N., Ku, G., Randle, J.C., Malva, J.O., Vezzani, A.. Inflammatory events in hippocampal slice cultures prime neuronal susceptibility to excitotoxic injury: a crucial role of P2X7 receptor-mediated IL-1beta release. J. Neurochem.. 2008; 106: 271-280 [OpenAIRE] [PubMed]

Bialas, A.R., Presumey, J., Das, A., van der Poel, C.E., Lapchak, P.H., Mesin, L., Victora, G., Tsokos, G.C., Mawrin, C., Herbst, R., Carroll, M.C.. Microglia-dependent synapse loss in type I interferon-mediated lupus. Nature. 2017; 546: 539-543 [PubMed]

Bischofberger, J., Engel, D., Li, L., Geiger, J.R.P., Jonas, P.. Patch-clamp recording from mossy fiber terminals in hippocampal slices. Nat. Protoc.. 2006; 1: 2075-2081 [OpenAIRE] [PubMed]

Bohlen, C.J., Bennett, F.C., Tucker, A.F., Collins, H.Y., Mulinyawe, S.B., Barres, B.A.. Diverse requirements for microglial survival, specification, and function revealed by defined-medium cultures. Neuron. 2017; 94: 759-773.e8 [OpenAIRE] [PubMed]

Boucsein, C., Zacharias, R., Färber, K., Pavlovic, S., Hanisch, U.K., Kettenmann, H.. Purinergic receptors on microglial cells: functional expression in acute brain slices and modulation of microglial activation in vitro. Eur. J. Neurosci.. 2003; 17: 2267-2276 [OpenAIRE] [PubMed]

Bradley, A., Anastassiadis, K., Ayadi, A., Battey, J.F., Bell, C., Birling, M.-C., Bottomley, J., Brown, S.D., Bürger, A., Bult, C.J.. The mammalian gene function resource: the International Knockout Mouse Consortium. Mamm. Genome. 2012; 23: 580-586 [OpenAIRE] [PubMed]

Brown, S.D., Moore, M.W.. The International Mouse Phenotyping Consortium: past and future perspectives on mouse phenotyping. Mamm. Genome. 2012; 23: 632-640 [OpenAIRE] [PubMed]

Butovsky, O., Jedrychowski, M.P., Moore, C.S., Cialic, R., Lanser, A.J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P.M., Doykan, C.E.. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat. Neurosci.. 2014; 17: 131-143 [OpenAIRE] [PubMed]

Charolidi, N., Schilling, T., Eder, C.. Microglial Kv1.3 channels and P2Y12 receptors differentially regulate cytokine and chemokine release from brain slices of young adult and aged mice. PLoS ONE. 2015; 10: e0128463 [OpenAIRE] [PubMed]

Chu, Y., Jin, X., Parada, I., Pesic, A., Stevens, B., Barres, B., Prince, D.A.. Enhanced synaptic connectivity and epilepsy in C1q knockout mice. Proc. Natl. Acad. Sci. USA. 2010; 107: 7975-7980 [OpenAIRE] [PubMed]

Condello, C., Yuan, P., Schain, A., Grutzendler, J.. Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques. Nat. Commun.. 2015; 6: 6176 [OpenAIRE] [PubMed]

Davalos, D., Grutzendler, J., Yang, G., Kim, J.V., Zuo, Y., Jung, S., Littman, D.R., Dustin, M.L., Gan, W.B.. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci.. 2005; 8: 752-758 [OpenAIRE] [PubMed]

Davalos, D., Ryu, J.K., Merlini, M., Baeten, K.M., Le Moan, N., Petersen, M.A., Deerinck, T.J., Smirnoff, D.S., Bedard, C., Hakozaki, H.. Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat. Commun.. 2012; 3: 1227 [OpenAIRE] [PubMed]

De Biase, L.M., Schuebel, K.E., Fusfeld, Z.H., Jair, K., Hawes, I.A., Cimbro, R., Zhang, H.Y., Liu, Q.R., Shen, H., Xi, Z.X.. Local cues establish and maintain region-specific phenotypes of basal ganglia microglia. Neuron. 2017; 95: 341-356.e6 [OpenAIRE] [PubMed]

De Simoni, A., Allen, N.J., Attwell, D.. Charge compensation for NADPH oxidase activity in microglia in rat brain slices does not involve a proton current. Eur. J. Neurosci.. 2008; 28: 1146-1156 [OpenAIRE] [PubMed]

66 references, page 1 of 5
Abstract
Summary Microglia exhibit two modes of motility: they constantly extend and retract their processes to survey the brain, but they also send out targeted processes to envelop sites of tissue damage. We now show that these motility modes differ mechanistically. We identify the two-pore domain channel THIK-1 as the main K+ channel expressed in microglia in situ. THIK-1 is tonically active, and its activity is potentiated by P2Y12 receptors. Inhibiting THIK-1 function pharmacologically or by gene knockout depolarizes microglia, which decreases microglial ramification and thus reduces surveillance, whereas blocking P2Y12 receptors does not affect membrane potential, ...
Subjects
free text keywords: General Neuroscience, Biology, Cytokine, medicine.medical_treatment, medicine, Receptor, Cell biology, Potassium channel, Motility, Inflammasome, medicine.drug, Membrane potential, Gene knockout, Microglia, medicine.anatomical_structure, Article, ATP, surveillance, interleukin-1β, ramification, THIK-1
Funded by
SNSF| Phases incommensurables, structures désordonnées, diffusion diffuse
Project
  • Funder: Swiss National Science Foundation (SNSF)
  • Project Code: 2000-046666
  • Funding stream: Project funding | Project funding (Div. I-III)
,
NIH| Function of Two-Pore Domain K Channels in Vascular Smooth Muscle
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R21HL098921-02
  • Funding stream: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
,
WT| Novel aspects of neurotransmitter signalling and its regulation by transporters in health and disease.
Project
  • Funder: Wellcome Trust (WT)
  • Project Code: 075232
  • Funding stream: Neuroscience and Mental Health
,
WT| The development, plasticity and pathology of myelinated CNS axons.
Project
  • Funder: Wellcome Trust (WT)
  • Project Code: 099222
  • Funding stream: Neuroscience and Mental Health
,
NIH| EDHF in the Cerebral Circulation
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01NS046666-05
  • Funding stream: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
66 references, page 1 of 5

Bernardino, L., Balosso, S., Ravizza, T., Marchi, N., Ku, G., Randle, J.C., Malva, J.O., Vezzani, A.. Inflammatory events in hippocampal slice cultures prime neuronal susceptibility to excitotoxic injury: a crucial role of P2X7 receptor-mediated IL-1beta release. J. Neurochem.. 2008; 106: 271-280 [OpenAIRE] [PubMed]

Bialas, A.R., Presumey, J., Das, A., van der Poel, C.E., Lapchak, P.H., Mesin, L., Victora, G., Tsokos, G.C., Mawrin, C., Herbst, R., Carroll, M.C.. Microglia-dependent synapse loss in type I interferon-mediated lupus. Nature. 2017; 546: 539-543 [PubMed]

Bischofberger, J., Engel, D., Li, L., Geiger, J.R.P., Jonas, P.. Patch-clamp recording from mossy fiber terminals in hippocampal slices. Nat. Protoc.. 2006; 1: 2075-2081 [OpenAIRE] [PubMed]

Bohlen, C.J., Bennett, F.C., Tucker, A.F., Collins, H.Y., Mulinyawe, S.B., Barres, B.A.. Diverse requirements for microglial survival, specification, and function revealed by defined-medium cultures. Neuron. 2017; 94: 759-773.e8 [OpenAIRE] [PubMed]

Boucsein, C., Zacharias, R., Färber, K., Pavlovic, S., Hanisch, U.K., Kettenmann, H.. Purinergic receptors on microglial cells: functional expression in acute brain slices and modulation of microglial activation in vitro. Eur. J. Neurosci.. 2003; 17: 2267-2276 [OpenAIRE] [PubMed]

Bradley, A., Anastassiadis, K., Ayadi, A., Battey, J.F., Bell, C., Birling, M.-C., Bottomley, J., Brown, S.D., Bürger, A., Bult, C.J.. The mammalian gene function resource: the International Knockout Mouse Consortium. Mamm. Genome. 2012; 23: 580-586 [OpenAIRE] [PubMed]

Brown, S.D., Moore, M.W.. The International Mouse Phenotyping Consortium: past and future perspectives on mouse phenotyping. Mamm. Genome. 2012; 23: 632-640 [OpenAIRE] [PubMed]

Butovsky, O., Jedrychowski, M.P., Moore, C.S., Cialic, R., Lanser, A.J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P.M., Doykan, C.E.. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat. Neurosci.. 2014; 17: 131-143 [OpenAIRE] [PubMed]

Charolidi, N., Schilling, T., Eder, C.. Microglial Kv1.3 channels and P2Y12 receptors differentially regulate cytokine and chemokine release from brain slices of young adult and aged mice. PLoS ONE. 2015; 10: e0128463 [OpenAIRE] [PubMed]

Chu, Y., Jin, X., Parada, I., Pesic, A., Stevens, B., Barres, B., Prince, D.A.. Enhanced synaptic connectivity and epilepsy in C1q knockout mice. Proc. Natl. Acad. Sci. USA. 2010; 107: 7975-7980 [OpenAIRE] [PubMed]

Condello, C., Yuan, P., Schain, A., Grutzendler, J.. Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques. Nat. Commun.. 2015; 6: 6176 [OpenAIRE] [PubMed]

Davalos, D., Grutzendler, J., Yang, G., Kim, J.V., Zuo, Y., Jung, S., Littman, D.R., Dustin, M.L., Gan, W.B.. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci.. 2005; 8: 752-758 [OpenAIRE] [PubMed]

Davalos, D., Ryu, J.K., Merlini, M., Baeten, K.M., Le Moan, N., Petersen, M.A., Deerinck, T.J., Smirnoff, D.S., Bedard, C., Hakozaki, H.. Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat. Commun.. 2012; 3: 1227 [OpenAIRE] [PubMed]

De Biase, L.M., Schuebel, K.E., Fusfeld, Z.H., Jair, K., Hawes, I.A., Cimbro, R., Zhang, H.Y., Liu, Q.R., Shen, H., Xi, Z.X.. Local cues establish and maintain region-specific phenotypes of basal ganglia microglia. Neuron. 2017; 95: 341-356.e6 [OpenAIRE] [PubMed]

De Simoni, A., Allen, N.J., Attwell, D.. Charge compensation for NADPH oxidase activity in microglia in rat brain slices does not involve a proton current. Eur. J. Neurosci.. 2008; 28: 1146-1156 [OpenAIRE] [PubMed]

66 references, page 1 of 5
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publication . Article . Other literature type . 2018

Microglial Ramification, Surveillance, and Interleukin-1β Release Are Regulated by the Two-Pore Domain K+ Channel THIK-1

Madry, Christian; Kyrargyri, Vasiliki; Arancibia-Cárcamo, I. Lorena; Jolivet, Renaud; Kohsaka, Shinichi; Bryan, Robert M.; Attwell, David;