Startseite Lebenswissenschaften Astrocytic potassium and calcium channels as integrators of the inflammatory and ischemic CNS microenvironment
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Astrocytic potassium and calcium channels as integrators of the inflammatory and ischemic CNS microenvironment

  • Samantha Schmaul

    Samantha Schmaul, Postdoctoral fellow, Focus Program Translational Neurosciences (FTN) fellow Mainz, Oct 2016 – now.

    ORCID logo
    , Nicholas Hanuscheck

    Nicholas Hanuscheck, PhD candidate, Transmed fellow Mainz, Dec 2020 – now.

    ORCID logo
    und Stefan Bittner

    Stefan Bittner W2-Professor, head of neuroimmunology, clinic and polyclinic of neurology university clinic Mainz, Member of the IZKF Münster, Jan 2012 - Dec 2014, Clinician Scientists SEED. projects, SEED03/12.

    ORCID logo EMAIL logo
Veröffentlicht/Copyright: 30. August 2021

Abstract

Astrocytes are key regulators of their surroundings by receiving and integrating stimuli from their local microenvironment, thereby regulating glial and neuronal homeostasis. Cumulating evidence supports a plethora of heterogenic astrocyte subpopulations that differ morphologically and in their expression patterns of receptors, transporters and ion channels, as well as in their functional specialisation. Astrocytic heterogeneity is especially relevant under pathological conditions. In experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), morphologically distinct astrocytic subtypes were identified and could be linked to transcriptome changes during different disease stages and regions. To allow for continuous awareness of changing stimuli across age and diseases, astrocytes are equipped with a variety of receptors and ion channels allowing the precise perception of environmental cues. Recent studies implicate the diverse repertoire of astrocytic ion channels – including transient receptor potential channels, voltage-gated calcium channels, inwardly rectifying K+ channels, and two-pore domain potassium channels – in sensing the brain state in physiology, inflammation and ischemia. Here, we review current evidence regarding astrocytic potassium and calcium channels and their functional contribution in homeostasis, neuroinflammation and stroke.


Corresponding author: Stefan Bittner, Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Centre of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, D-55131 Mainz, Germany, E-mail:
Samantha Schmaul and Nicholas Hanuscheck contributed equally to this work. This article is a contribution to the issue highlighting the 25th Anniversary of the Interdisciplinary Centre for Clinical Research (IZKF) Münster.

Award Identifier / Grant number: SFB/TR-128

About the authors

Samantha Schmaul

Samantha Schmaul, Postdoctoral fellow, Focus Program Translational Neurosciences (FTN) fellow Mainz, Oct 2016 – now.

Nicholas Hanuscheck

Nicholas Hanuscheck, PhD candidate, Transmed fellow Mainz, Dec 2020 – now.

Stefan Bittner

Stefan Bittner W2-Professor, head of neuroimmunology, clinic and polyclinic of neurology university clinic Mainz, Member of the IZKF Münster, Jan 2012 - Dec 2014, Clinician Scientists SEED. projects, SEED03/12.

Acknowledgements

We thank Cheryl Ernest for proofreading of the manuscript.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by grants from the German Research Foundation (DFG, SFB/TR-128 to S.B.); Figure 1 was created with BioRender.com.

  3. Conflict of interest statement: The authors declare no conflict of interest.

References

Banerjee, A., Ghatak, S., and Sikdar, S.K. (2016). l-Lactate mediates neuroprotection against ischaemia by increasing TREK1 channel expression in rat hippocampal astrocytes in vitro. J. Neurochem. 138: 265–281, https://doi.org/10.1111/jnc.13638.Suche in Google Scholar PubMed

Bay, V. and Butt, A.M. (2012). Relationship between glial potassium regulation and axon excitability: a role for glial Kir4.1 channels. Glia 60: 651–660, https://doi.org/10.1002/glia.22299.Suche in Google Scholar PubMed

Bazargani, N. and Attwell, D. (2017). Amines, astrocytes, and arousal. Neuron 94: 228–231, https://doi.org/10.1016/j.neuron.2017.03.035.Suche in Google Scholar PubMed

Beskina, O., Miller, A., Mazzocco-Spezzia, A., Pulina, M.V., and Golovina, V.A. (2007). Mechanisms of interleukin-1β-induced Ca 2+ signals in mouse cortical astrocytes: roles of store- and receptor-operated Ca 2+ entry. Am. J. Physiol. Cell Physiol. 293: C1103–C1111, https://doi.org/10.1152/ajpcell.00249.2007.Suche in Google Scholar PubMed

Bittner, S., Budde, T., Wiendl, H., and Meuth, S.G. (2010). From the background to the spotlight: TASK channels in pathological conditions. Brain Pathol. 20: 999–1009, https://doi.org/10.1111/j.1750-3639.2010.00407.x.Suche in Google Scholar PubMed PubMed Central

Bittner, S., Ruck, T., Fernández-Orth, J., and Meuth, S.G. (2014). TREK-king the blood-brain-barrier. J. Neuroimmune Pharmacol. 9: 293–301, https://doi.org/10.1007/s11481-014-9530-8.Suche in Google Scholar PubMed

Bittner, S., Ruck, T., Schuhmann, M.K., Herrmann, A.M., Maati, H.M.O., Bobak, N., Göbel, K., Langhauser, F., Stegner, D., Ehling, P., et al. (2013). Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS. Nat. Med. 19: 1161–1165, doi:https://doi.org/10.1038/nm.3303.Suche in Google Scholar PubMed

Bölcskei, K., Kriszta, G., Sághy, É., Payrits, M., Sipos, É., Vranesics, A., Berente, Z., Ábrahám, H., Ács, P., Komoly, S., et al. (2018). Behavioural alterations and morphological changes are attenuated by the lack of TRPA1 receptors in the cuprizone-induced demyelination model in mice. J. Neuroimmunol. 320: 1–10, doi:https://doi.org/10.1016/j.jneuroim.2018.03.020.Suche in Google Scholar PubMed

Borggrewe, M., Grit, C., Vainchtein, I.D., Brouwer, N., Wesseling, E.M., Laman, J.D., Eggen, B.J.L., Kooistra, S.M., and Boddeke, E.W.G.M. (2021). Regionally diverse astrocyte subtypes and their heterogeneous response to EAE. Glia 69: 1140–1154, doi:https://doi.org/10.1002/glia.23954.Suche in Google Scholar PubMed PubMed Central

Bozic, I., Savic, D., Milosevic, A., Janjic, M., Laketa, D., Tesovic, K., Bjelobaba, I., Jakovljevic, M., Nedeljkovic, N., Pekovic, S., et al. (2019). The potassium channel Kv1.5 expression alters during experimental autoimmune encephalomyelitis. Neurochem. Res. 44: 2733–2745, doi:https://doi.org/10.1007/s11064-019-02892-4.Suche in Google Scholar PubMed

Bozic, I., Tesovic, K., Laketa, D., Adzic, M., Jakovljevic, M., Bjelobaba, I., Savic, D., Nedeljkovic, N., Pekovic, S., and Lavrnja, I. (2018). Voltage gated potassium channel Kv1.3 is upregulated on activated astrocytes in experimental autoimmune encephalomyelitis. Neurochem. Res. 43: 1020–1034, doi:https://doi.org/10.1007/s11064-018-2509-8.Suche in Google Scholar PubMed

Brambilla, R. (2019). The contribution of astrocytes to the neuroinflammatory response in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathol. 137: 757–783, https://doi.org/10.1007/s00401-019-01980-7.Suche in Google Scholar PubMed PubMed Central

Brambilla, R., Morton, P.D., Ashbaugh, J.J., Karmally, S., Lambertsen, K.L., and Bethea, J.R. (2014). Astrocytes play a key role in EAE pathophysiology by orchestrating in the CNS the inflammatory response of resident and peripheral immune cells and by suppressing remyelination. Glia 62: 452–467, https://doi.org/10.1002/glia.22616.Suche in Google Scholar PubMed

Brosnan, C.F. and Raine, C.S. (2013). The astrocyte in multiple sclerosis revisited. Glia 9: 1–13, https://doi.org/10.1002/glia.22443.Suche in Google Scholar PubMed

Butenko, O., Dzamba, D., Benesova, J., Honsa, P., Benfenati, V., Rusnakova, V., Ferroni, S., and Anderova, M. (2012). The increased activity of TRPV4 channel in the astrocytes of the adult rat Hippocampus after cerebral hypoxia/ischemia. PloS One 7: e39959, doi:https://doi.org/10.1371/journal.pone.0039959.Suche in Google Scholar PubMed PubMed Central

Caspani, O. and Heppenstall, P.A. (2009). TRPA1 and cold transduction: an unresolved issue? J. Gen. Physiol. 133: 245–249, https://doi.org/10.1085/jgp.200810136.Suche in Google Scholar PubMed PubMed Central

Cekanaviciute, E. and Buckwalter, M.S. (2016). Astrocytes: integrative regulators of neuroinflammation in stroke and other neurological diseases. Neurotherapeutics 13: 685–701, https://doi.org/10.1007/s13311-016-0477-8.Suche in Google Scholar PubMed PubMed Central

Chavda, V., Madhwani, K., and Chaurasia, B. (2021). Stroke and immunotherapy: potential mechanisms and its implications as immune‐therapeutics. Eur. J. Neurosci. 54: 15224, https://doi.org/10.1111/ejn.15224.Suche in Google Scholar PubMed

Cheli, V.T., Santiago González, D.A., Smith, J., Spreuer, V., Murphy, G.G., and Paez, P.M. (2016). L-type voltage-operated calcium channels contribute to astrocyte activation in vitro. Glia 64: 1396–1415, https://doi.org/10.1002/glia.23013.Suche in Google Scholar PubMed PubMed Central

Chen, X., Lu, M., He, X., Ma, L., Birnbaumer, L., and Liao, Y. (2017). TRPC3/6/7 knockdown protects the brain from cerebral ischemia injury via astrocyte apoptosis inhibition and effects on NF-кB translocation. Mol. Neurobiol. 54: 7555–7566, https://doi.org/10.1007/s12035-016-0227-2.Suche in Google Scholar PubMed

Clapham, D.E. (2003). TRP channels as cellular sensors. Nature 426: 517–524, https://doi.org/10.1038/nature02196.Suche in Google Scholar PubMed

Dalenogare, D.P., Theisen, M.C., Peres, D.S., Fialho, M.F.P., Lückemeyer, D.D., Antoniazzi, C.T.D., Kudsi, S.Q., Ferreira, M.A., Ritter, C.S., Ferreira, J., et al. (2020). TRPA1 activation mediates nociception behaviors in a mouse model of relapsing-remitting experimental autoimmune encephalomyelitis. Exp. Neurol. 328: 113241, doi:https://doi.org/10.1016/j.expneurol.2020.113241.Suche in Google Scholar PubMed

Deemyad, T., Lüthi, J., and Spruston, N. (2018). Astrocytes integrate and drive action potential firing in inhibitory subnetworks. Nat. Commun. 9: 1–13, https://doi.org/10.1038/s41467-018-06338-3.Suche in Google Scholar PubMed PubMed Central

Diaz-Castro, B., Gangwani, M.R., Yu, X., Coppola, G., and Khakh, B.S. (2019). Astrocyte molecular signatures in Huntington’s disease. Sci. Transl. Med. 11: eaaw8546, https://doi.org/10.1126/scitranslmed.aaw8546.Suche in Google Scholar PubMed

Djukic, B., Casper, K.B., Philpot, B.D., Chin, L.S., and McCarthy, K.D. (2007). Conditional knock-out of Kir4.1 leads to glial membrane depolarization, inhibition of potassium and glutamate uptake, and enhanced short-term synaptic potentiation. J. Neurosci. 27: 11354–11365, https://doi.org/10.1523/jneurosci.0723-07.2007.Suche in Google Scholar

Du, Y., Kiyoshi, C.M., Wang, Q., Wang, W., Ma, B., Alford, C.C., Zhong, S., Wan, Q., Chen, H., Lloyd, E.E., et al. (2016). Genetic deletion of TREK-1 or TWIK-1/TREK-1 potassium channels does not alter the basic electrophysiological properties of mature hippocampal astrocytes in situ. Front. Cell. Neurosci. 10: 13, doi:https://doi.org/10.3389/fncel.2016.00013.Suche in Google Scholar PubMed PubMed Central

Dvorzhak, A., Vagner, T., Kirmse, K., and Grantyn, R. (2016). Functional indicators of glutamate transport in single striatal astrocytes and the influence of Kir4.1 in normal and huntington mice. J. Neurosci. 36: 4959–4975, https://doi.org/10.1523/jneurosci.0316-16.2016.Suche in Google Scholar PubMed PubMed Central

Ehling, P., Cerina, M., Budde, T., Meuth, S.G., and Bittner, S. (2015). The CNS under pathophysiologic attack – examining the role of K2P channels. Eur. J. Physiol. 467: 959–972, https://doi.org/10.1007/s00424-014-1664-2.Suche in Google Scholar PubMed

Ellwardt, E. and Zipp, F. (2014). Molecular mechanisms linking neuroinflammation and neurodegeneration in MS. Exp. Neurol. 262: 8–17, https://doi.org/10.1016/j.expneurol.2014.02.006.Suche in Google Scholar PubMed

Escartin, C., Galea, E., Lakatos, A., O’Callaghan, J.P., Petzold, G.C., Serrano-Pozo, A., Steinhäuser, C., Volterra, A., Carmignoto, G., Agarwal, A., et al. (2021). Reactive astrocyte nomenclature, definitions, and future directions. Nat. Neurosci. 24: 312–325.10.1038/s41593-020-00783-4Suche in Google Scholar PubMed PubMed Central

Everaerts, W., Gees, M., Alpizar, Y.A., Farre, R., Leten, C., Apetrei, A., Dewachter, I., Van Leuven, F., Vennekens, R., De Ridder, D., et al. (2011). The capsaicin receptor TRPV1 is a crucial mediator of the noxious effects of mustard oil. Curr. Biol. 21: 316–321, doi:https://doi.org/10.1016/j.cub.2011.01.031.Suche in Google Scholar PubMed

Golovina, V.A. (2005). Visualization of localized store-operated calcium entry in mouse astrocytes. Close proximity to the endoplasmic reticulum. J. Physiol. 564: 737–749, https://doi.org/10.1113/jphysiol.2005.085035.Suche in Google Scholar PubMed PubMed Central

Götz, S., Bribian, A., López‐Mascaraque, L., Götz, M., Grothe, B., and Kunz, L. (2021). Heterogeneity of astrocytes: electrophysiological properties of juxtavascular astrocytes before and after brain injury. Glia 69: 346–361, https://doi.org/10.1002/glia.23900.Suche in Google Scholar PubMed

Haj-Yasein, N.N., Jensen, V., Vindedal, G.F., Gundersen, G.A., Klungland, A., Ottersen, O.P., Hvalby, Ø., and Nagelhus, E.A. (2011). Evidence that compromised K+ spatial buffering contributes to the epileptogenic effect of mutations in the human kir4.1 gene (KCNJ10). Glia 59: 1635–1642, doi:https://doi.org/10.1002/glia.21205.Suche in Google Scholar PubMed

Hamilton, N.B., Kolodziejczyk, K., Kougioumtzidou, E., and Attwell, D. (2016). Proton-gated Ca2+-permeable TRP channels damage myelin in conditions mimicking ischaemia. Nature 529: 1–14, https://doi.org/10.1038/nature16519.Suche in Google Scholar PubMed PubMed Central

Heurteaux, C., Guy, N., Laigle, C., Blondeau, N., Duprat, F., Mazzuca, M., Lang-Lazdunski, L., Widmann, C., Zanzouri, M., Romey, G., et al. (2004). TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO J. 23: 2684–2695, doi:https://doi.org/10.1038/sj.emboj.7600234.Suche in Google Scholar PubMed PubMed Central

Imamura, M., Higuchi, O., Maeda, Y., Mukaino, A., Ueda, M., Matsuo, H., and Nakane, S. (2020). Anti-Kir4.1 antibodies in multiple sclerosis: specificity and pathogenicity. Int. J. Mol. Sci. 21: 1–12, doi:https://doi.org/10.3390/ijms21249632.Suche in Google Scholar PubMed PubMed Central

Jukkola, P., Guerrero, T., Gray, V., and Gu, C. (2013). Astrocytes differentially respond to inflammatory autoimmune insults and imbalances of neural activity. Acta Neuropathol. Commun. 1: 70, https://doi.org/10.1186/2051-5960-1-70.Suche in Google Scholar PubMed PubMed Central

Jukkola, P.I., Lovett-Racke, A.E., Zamvil, S.S., and Gu, C. (2012). K+ channel alterations in the progression of experimental autoimmune encephalomyelitis. Neurobiol. Dis. 47: 280–293, https://doi.org/10.1016/j.nbd.2012.04.012.Suche in Google Scholar PubMed PubMed Central

Kim, A., Jung, H., Kim, S., Choi, M., Park, J., Lee, S.G., and Hwang, E.M. (2020). Astrocytic AEG‐1 regulates expression of TREK‐1 under acute hypoxia. Cell Biochem. Funct. 38: 167–175, doi:https://doi.org/10.1002/cbf.3469.Suche in Google Scholar PubMed

Kim, R.Y., Hoffman, A.S., Itoh, N., Ao, Y., Spence, R., Sofroniew, M.V., and Voskuhl, R.R. (2014). Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis. J. Neuroimmunol. 274: 53–61, doi:https://doi.org/10.1016/j.jneuroim.2014.06.009.Suche in Google Scholar PubMed PubMed Central

Kozai, D., Ogawa, N., and Mori, Y. (2014). Redox regulation of transient receptor potential channels. Antioxidants Redox Signal. 21: 971–986, https://doi.org/10.1089/ars.2013.5616.Suche in Google Scholar PubMed

Kriegstein, A.R. and Götz, M. (2003). Radial glia diversity: a matter of cell fate. Glia 43: 37–43.10.1002/glia.10250Suche in Google Scholar PubMed

Kriszta, G., Nemes, B., Sándor, Z., Ács, P., Komoly, S., Berente, Z., Bölcskei, K., and Pintér, E. (2019). Investigation of cuprizone-induced demyelination in mGFAP-driven conditional transient receptor potential ankyrin 1 (TRPA1) receptor knockout mice. Cells 9: 81, doi:https://doi.org/10.3390/cells9010081.Suche in Google Scholar PubMed PubMed Central

Li, X., Wu, G., Yang, Y., Fu, S., Liu, X., Kang, H., Yang, X., Su, X.C., and Shen, Y. (2017). Calmodulin dissociates the STIM1-Orai1 complex and STIM1 oligomers. Nat. Commun. 8: 1042, doi:https://doi.org/10.1038/s41467-017-01135-w.Suche in Google Scholar PubMed PubMed Central

Liddelow, S.A. and Barres, B.A. (2017). Reactive astrocytes: production, function, and therapeutic potential. Immunity 46: 957–967, https://doi.org/10.1016/j.immuni.2017.06.006.Suche in Google Scholar PubMed

Liddelow, S.A., Guttenplan, K.A., Clarke, L.E., Bennett, F.C., Bohlen, C.J., Schirmer, L., Bennett, M.L., Münch, A.E., Chung, W.S., Peterson, T.C., et al. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nat. Publ. Gr. 541: 481–487, doi:https://doi.org/10.1038/nature21029.Suche in Google Scholar PubMed PubMed Central

Lindsay, M.P., Norrving, B., Sacco, R.L., Brainin, M., Hacke, W., Martins, S., Pandian, J., and Feigin, V. (2019). World Stroke Organization (WSO): global stroke fact sheet 2019. Int. J. Stroke 14: 806–817, doi:https://doi.org/10.1177/1747493019881353.Suche in Google Scholar PubMed

Liu, Y., Sun, Q., Chen, X., Jing, L., Wang, W., Yu, Z., Zhang, G., and Xie, M. (2014). Linolenic acid provides multi-cellular protective effects after photothrombotic cerebral ischemia in rats. Neurochem. Res. 39: 1797–1808, doi:https://doi.org/10.1007/s11064-014-1390-3.Suche in Google Scholar PubMed

Lu, L., Zhang, G., Song, C., Wang, X., Qian, W., Wang, Z., Liu, Y., Gong, S., and Zhou, S. (2017). Arachidonic acid has protective effects on oxygen-glucose deprived astrocytes mediated through enhancement of potassium channel TREK-1 activity. Neurosci. Lett. 636: 241–247, doi:https://doi.org/10.1016/j.neulet.2016.11.034.Suche in Google Scholar PubMed

Ma, Z., Stork, T., Bergles, D.E., and Freeman, M.R. (2016). Neuromodulators signal through astrocytes to alter neural circuit activity and behaviour. Nature 539: 428–432, https://doi.org/10.1038/nature20145.Suche in Google Scholar PubMed PubMed Central

Matthias, K., Kirchhoff, F., Seifert, G., Hüttmann, K., Matyash, M., Kettenmann, H., and Steinhäuser, C. (2003). Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippocampus. J. Neurosci. 23: 1750–1758, doi:https://doi.org/10.1523/jneurosci.23-05-01750.2003.Suche in Google Scholar

Mayo, L., Trauger, S.A., Blain, M., Nadeau, M., Patel, B., Alvarez, J.I., Mascanfroni, I.D., Yeste, A., Kivisäkk, P., Kallas, K., et al. (2014). Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nat. Med. 20: 1147–1156, doi:https://doi.org/10.1038/nm.3681.Suche in Google Scholar PubMed PubMed Central

Mercado, F., Almanza, A., Rubio, N., and Soto, E. (2018). Kir 4.1 inward rectifier potassium channel is upregulated in astrocytes in a murine multiple sclerosis model. Neurosci. Lett. 677: 88–93, https://doi.org/10.1016/j.neulet.2018.04.052.Suche in Google Scholar PubMed

Mi Hwang, E., Kim, E., Yarishkin, O., Ho Woo, D., Han, K.S., Park, N., Bae, Y., Woo, J., Kim, D., Park, M., et al. (2014). A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes. Nat. Commun. 5: 1–15, doi:https://doi.org/10.1038/ncomms4227.Suche in Google Scholar PubMed

Montell, C. (2005). The TRP superfamily of cation channels. Sci. STKE 2005: re3, https://doi.org/10.1126/stke.2722005re3.Suche in Google Scholar PubMed

Moreno, C., Sampieri, A., Vivas, O., Peña-Segura, C., and Vaca, L. (2012). STIM1 and Orai1 mediate thrombin-induced Ca2+ influx in rat cortical astrocytes. Cell Calcium 52: 457–467, https://doi.org/10.1016/j.ceca.2012.08.004.Suche in Google Scholar PubMed

Munakata, M., Shirakawa, H., Nagayasu, K., Miyanohara, J., Miyake, T., Nakagawa, T., Katsuki, H., and Kaneko, S. (2013). Transient receptor potential canonical 3 inhibitor pyr3 improves outcomes and attenuates Astrogliosis after Intracerebral hemorrhage in mice. Stroke 44: 1981–1987, doi:https://doi.org/10.1161/strokeaha.113.679332.Suche in Google Scholar PubMed

Murakami, S. and Kurachi, Y. (2016). Mechanisms of astrocytic K+ clearance and swelling under high extracellular K+ concentrations. J. Physiol. Sci. 66: 127–142, https://doi.org/10.1007/s12576-015-0404-5.Suche in Google Scholar PubMed

Nair, A., Frederick, T.J., and Miller, S.D. (2008). Astrocytes in multiple sclerosis: a product of their environment. Cell. Mol. Life Sci. 65: 2702–2720, https://doi.org/10.1007/s00018-008-8059-5.Suche in Google Scholar PubMed PubMed Central

Nassini, R., Materazzi, S., Benemei, S., and Geppetti, P. (2014). The TRPA1 channel in inflammatory and neuropathic pain and migraine. Rev. Physiol. Biochem. Pharmacol. 167: 1–43, https://doi.org/10.1007/112_2014_18.Suche in Google Scholar PubMed

Nilius, B. and Owsianik, G. (2011). The transient receptor potential family of ion channels. Genome Biol. 12: 218, https://doi.org/10.1186/gb-2011-12-3-218.Suche in Google Scholar PubMed PubMed Central

Nwaobi, S.E., Cuddapah, V.A., Patterson, K.C., Randolph, A.C., and Olsen, M.L. (2016). The role of glial-specific Kir4.1 in normal and pathological states of the CNS. Acta Neuropathol. 132: 1, https://doi.org/10.1007/s00401-016-1553-1.Suche in Google Scholar PubMed PubMed Central

Oberheim, N.A., Goldman, S.A., and Nedergaard, M. (2012). Heterogeneity of astrocytic form and function. Methods Mol. Biol. 814: 23–45, https://doi.org/10.1007/978-1-61779-452-0_3.Suche in Google Scholar PubMed PubMed Central

Ohara, H. and Nabika, T. (2016). A nonsense mutation of Stim1 identified in stroke-prone spontaneously hypertensive rats decreased the store-operated calcium entry in astrocytes. Biochem. Biophys. Res. Commun. 476: 406–411, https://doi.org/10.1016/j.bbrc.2016.05.134.Suche in Google Scholar PubMed

Olsen, M.L., Khakh, B.S., Skatchkov, S.N., Zhou, M., Lee, C.J., and Rouach, N. (2015). New insights on astrocyte ion channels: critical for homeostasis and neuron-glia signaling. J. Neurosci. 35: 13827–13835, https://doi.org/10.1523/jneurosci.2603-15.2015.Suche in Google Scholar

Paltser, G., Liu, X.J., Yantha, J., Winer, S., Tsui, H., Wu, P., Maezawa, Y., Cahill, L.S., Laliberté, C.L., Ramagopalan, S.V., et al. (2013). TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis. Mol. Med. 19: 149–159, doi:https://doi.org/10.2119/molmed.2012.00329.Suche in Google Scholar PubMed PubMed Central

Papanikolaou, M., Lewis, A., and Butt, A.M. (2017). Store-operated calcium entry is essential for glial calcium signalling in CNS white matter. Brain Struct. Funct. 222: 2993–3005, https://doi.org/10.1007/s00429-017-1380-8.Suche in Google Scholar PubMed PubMed Central

Parpura, V., Grubišic, V., and Verkhratsky, A. (2011). Ca2+ sources for the exocytotic release of glutamate from astrocytes. Biochim. Biophys. Acta Mol. Cell Res. 1813: 984–991, https://doi.org/10.1016/j.bbamcr.2010.11.006.Suche in Google Scholar PubMed

Pestana, F., Edwards-Faret, G., Belgard, T.G., Martirosyan, A., and Holt, M.G. (2020). No longer underappreciated: the emerging concept of astrocyte heterogeneity in neuroscience. Brain Sci. 10: 168, https://doi.org/10.3390/brainsci10030168.Suche in Google Scholar PubMed PubMed Central

Pinggera, A. and Striessnig, J. (2016). Cav1.3 (CACNA1D) L-type Ca2+ channel dysfunction in CNS disorders. J. Physiol. 594: 5839–5849, https://doi.org/10.1113/jp270672.Suche in Google Scholar

Pivonkova, H., Benesova, J., Butenko, O., Chvatal, A., and Anderova, M. (2010). Impact of global cerebral ischemia on K+ channel expression and membrane properties of glial cells in the rat hippocampus. Neurochem. Int. 57: 783–794, https://doi.org/10.1016/j.neuint.2010.08.016.Suche in Google Scholar PubMed

Rakers, C., Schleif, M., Blank, N., Matušková, H., Ulas, T., Händler, K., Torres, S.V., Schumacher, T., Tai, K., Schultze, J.L., et al. (2019). Stroke target identification guided by astrocyte transcriptome analysis. Glia 67: 619–633, doi:https://doi.org/10.1002/glia.23544.Suche in Google Scholar PubMed

Reyes, R.C., Verkhratsky, A., and Parpura, V. (2013). TRPC1-mediated Ca2+ and Na+ signalling in astroglia: differential filtering of extracellular cations. Cell Calcium 54: 120–125, https://doi.org/10.1016/j.ceca.2013.05.005.Suche in Google Scholar PubMed PubMed Central

Ritter, C., Dalenogare, D.P., de Almeida, A.S., Pereira, V.L., Pereira, G.C., Fialho, M.F.P., Lückemeyer, D.D., Antoniazzo, C.T., Kudsi, S.Q., Ferreira, J., et al. (2020). Nociception in a progressive multiple sclerosis model in mice is dependent on spinal TRPA1 channel activation. Mol. Neurobiol. 57: 2420–2435, doi:https://doi.org/10.1007/s12035-020-01891-9.Suche in Google Scholar PubMed

Rivera-Pagán, A.F., Rivera-Aponte, D.E., Melnik-Martínez, K.V., Zayas-Santiago, A., Kucheryavykh, L.Y., Martins, A.H., Cubano, L.A., Skatchkov, S.N., and Eaton, M.J. (2015). Up-regulation of TREK-2 potassium channels in cultured astrocytes requires de novo protein synthesis: relevance to localization of TREK-2 channels in astrocytes after transient cerebral ischemia. PloS One 10: e0125195, doi:https://doi.org/10.1371/journal.pone.0125195.Suche in Google Scholar PubMed PubMed Central

Rothhammer, V., Borucki, D.M., Tjon, E.C., Takenaka, M.C., Chao, C.-C., Ardura-Fabregat, A., De Lima, K.A., Gutiérrez-Vázquez, C., Hewson, P., Staszewski, O., et al. (2018). Microglial control of astrocytes in response to microbial metabolites. Nature 557: 724–728, doi:https://doi.org/10.1038/s41586-018-0119-x.Suche in Google Scholar PubMed PubMed Central

Rubio, N., Almanza, A., Mercado, F., Arévalo, M.-Á.T., Garcia-Segura, L.M.M., Vega, R., and Soto, E. (2013). Upregulation of voltage-gated Ca2+ channels in mouse astrocytes infected with Theiler’s murine encephalomyelitis virus (TMEV). Neuroscience 247: 309–318, doi:https://doi.org/10.1016/j.neuroscience.2013.05.049.Suche in Google Scholar PubMed

Ryoo, K. and Park, J.-Y. (2016). Two-pore domain potassium channels in astrocytes. Exp. Neurobiol. 25: 222–232, https://doi.org/10.5607/en.2016.25.5.222.Suche in Google Scholar PubMed PubMed Central

Saghy, E., Sipos, E., Acs, P., Bölcskei, K., Pohoczky, K., Kemeny, A., Sandor, Z., Szoke, E., Setalo Jr, G., Komoly, S., et al. (2016). TRPA1 deficiency is protective in cuprizone-induced demyelination – a new target against oligodendrocyte apoptosis. Glia 64: 1–15, doi:https://doi.org/10.1002/glia.23051.Suche in Google Scholar PubMed

Sanmarco, L.M., Wheeler, M.A., Gutiérrez-Vázquez, C., Polonio, C.M., Linnerbauer, M., Pinho-Ribeiro, F.A., Li, Z., Giovannoni, F., Batterman, K.V., Scalisi, G., et al. (2021). Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes. Nature 590: 473, doi:https://doi.org/10.1038/s41586-020-03116-4.Suche in Google Scholar PubMed PubMed Central

Sawada, Y., Hosokawa, H., Matsumura, K., and Kobayashi, S. (2008). Activation of transient receptor potential ankyrin 1 by hydrogen peroxide. Eur. J. Neurosci. 27: 1131–1142, https://doi.org/10.1111/j.1460-9568.2008.06093.x.Suche in Google Scholar PubMed

Schirmer, L., Srivastava, R., Kalluri, S.R., Böttinger, S., Herwerth, M., Carassiti, D., Srivastava, B., Gempt, J., Schlegel, J., Kuhlmann, T., et al. (2014). Differential loss of KIR4.1 immunoreactivity in multiple sclerosis lesions. Ann. Neurol. 75: 810–828, doi:https://doi.org/10.1002/ana.24168.Suche in Google Scholar PubMed

Secondo, A., Bagetta, G., and Amantea, D. (2018). On the role of store-operated calcium entry in acute and chronic neurodegenerative diseases. Front Mol Neurosci 11: 87, https://doi.org/10.3389/fnmol.2018.00087.Suche in Google Scholar PubMed PubMed Central

Seifert, G., Henneberger, C., and Steinhäuser, C. (2018). Diversity of astrocyte potassium channels: an update. Brain Res. Bull. 136: 26–36, https://doi.org/10.1016/j.brainresbull.2016.12.002.Suche in Google Scholar PubMed

Shibasaki, K., Ikenaka, K., Tamalu, F., Tominaga, M., and Ishizaki, Y. (2014). A novel subtype of astrocytes expressing TRPV4 (Transient Receptor Potential Vanilloid 4) regulates neuronal excitability via release of gliotransmitters. J. Biol. Chem. 289: 14470–14480, https://doi.org/10.1074/jbc.m114.557132.Suche in Google Scholar PubMed PubMed Central

Shibasaki, K., Ishizaki, Y., and Mandadi, S. (2013). Astrocytes express functional TRPV2 ion channels. Biochem. Biophys. Res. Commun. 441: 327–332, https://doi.org/10.1016/j.bbrc.2013.10.046.Suche in Google Scholar PubMed

Shibata, M. and Tang, C. (2020). Implications of transient receptor potential cation channels in migraine pathophysiology. Neurosci. Bull. 37: 103–116, https://doi.org/10.1007/s12264-020-00569-5.Suche in Google Scholar PubMed PubMed Central

Shigetomi, E., Tong, X., Kwan, K.Y., Corey, D.P., and Khakh, B.S. (2011). TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy through GAT-3. Nat. Neurosci. 15: 70–80, https://doi.org/10.1038/nn.3000.Suche in Google Scholar PubMed PubMed Central

Shimizu, S., Takahashi, N., and Mori, Y. (2014). TRPs as chemosensors (ROS, RNS, RCS, gasotransmitters). Handb. Exp. Pharmacol. 223: 767–794, https://doi.org/10.1007/978-3-319-05161-1_3.Suche in Google Scholar PubMed

Shirakawa, H., Katsumoto, R., Iida, S., Miyake, T., Higuchi, T., Nagashima, T., Nagayasu, K., Nakagawa, T., and Kaneko, S. (2017). Sphingosine-1-phosphate induces Ca2+ signaling and CXCL1 release via TRPC6 channel in astrocytes. Glia 65: 1005–1016, doi:https://doi.org/10.1002/glia.23141.Suche in Google Scholar

Shirakawa, H., Sakimoto, S., Nakao, K., Sugishita, A., Konno, M., Iida, S., Kusano, A., Hashimoto, E., Nakagawa, T., and Kaneko, S. (2010). Transient receptor potential canonical 3 (TRPC3) mediates thrombin-induced astrocyte activation and upregulates its own expression in cortical astrocytes. J. Neurosci. 30: 13116–13129, doi:https://doi.org/10.1523/jneurosci.1890-10.2010.Suche in Google Scholar

Sibille, J., Pannasch, U., and Rouach, N. (2014). Astroglial potassium clearance contributes to short-term plasticity of synaptically evoked currents at the tripartite synapse. J. Physiol. 592: 87–102, https://doi.org/10.1113/jphysiol.2013.261735.Suche in Google Scholar

Sofroniew, M.V. and Vinters, H.V. (2010). Astrocytes: biology and pathology. Acta Neuropathol. 119: 7–35, https://doi.org/10.1007/s00401-009-0619-8.Suche in Google Scholar

Srivastava, R., Aslam, M., Kalluri, S.R., Schirmer, L., Buck, D., Tackenberg, B., Rothhammer, V., Chan, A., Gold, R., Berthele, A., et al. (2012). Potassium channel KIR4.1 as an immune target in multiple sclerosis. N. Engl. J. Med. 367: 115–123, doi:https://doi.org/10.1056/nejmoa1110740.Suche in Google Scholar

Takahashi, N., Mizuno, Y., Kozai, D., Yamamoto, S., Kiyonaka, S., Shibata, T., Uchida, K., and Mori, Y. (2008). Molecular characterization of TRPA1 channel activation by cysteine-reactive inflammatory mediators. Channels 2: 287–298, doi:https://doi.org/10.4161/chan.2.4.6745.Suche in Google Scholar

Takahashi, N. and Mori, Y. (2011). TRP channels as sensors and signal integrators of redox status changes. Front. Pharmacol. 2: 58, https://doi.org/10.3389/fphar.2011.00058.Suche in Google Scholar

Thompson, A.J., Toosy, A.T., and Ciccarelli, O. (2010). Pharmacological management of symptoms in multiple sclerosis: current approaches and future directions. Lancet Neurol. 9: 1182–1199, https://doi.org/10.1016/s1474-4422(10)70249-0.Suche in Google Scholar

Toth, A.B., Hori, K., Novakovic, M.M., Bernstein, N.G., Lambot, L., and Prakriya, M. (2019). CRAC channels regulate astrocyte Ca2+ signaling and gliotransmitter release to modulate hippocampal GABAergic transmission. Sci. Signal. 12: eaaw5450, https://doi.org/10.1126/scisignal.aaw5450.Suche in Google Scholar PubMed PubMed Central

Uchiyama, M., Nakao, A., Kurita, Y., Fukushi, I., Takeda, K., Numata, T., Tran, H.N., Sawamura, S., Ebert, M., Kurokawa, T., et al. (2020). O2-dependent protein internalization underlies astrocytic sensing of acute hypoxia by restricting multimodal TRPA1 channel responses. Curr. Biol. 30: 3378–3396.e7, doi:https://doi.org/10.1016/j.cub.2020.06.047.Suche in Google Scholar PubMed

Vennekens, R., Menigoz, A., and Nilius, B. (2012). TRPs in the brain. Rev. Physiol. Biochem. Pharmacol. 163: 27–64, https://doi.org/10.1007/112_2012_8.Suche in Google Scholar PubMed

Verkhratsky, A. and Nedergaard, M. (2016). The homeostatic astroglia emerges from evolutionary specialization of neural cells. Philos Trans R Soc Lond B Biol Sci 371: 20150428, https://doi.org/10.1098/rstb.2015.0428.Suche in Google Scholar PubMed PubMed Central

Verkhratsky, A. and Parpura, V. (2014). Store-operated calcium entry in neuroglia. Neurosci. Bull. 30: 125–133, https://doi.org/10.1007/s12264-013-1343-x.Suche in Google Scholar PubMed PubMed Central

Verkhratsky, A., Trebak, M., Perocchi, F., Khananshvili, D., and Sekler, I. (2018). Crosslink between calcium and sodium signalling. Exp. Physiol. 103: 157–169, https://doi.org/10.1113/ep086534.Suche in Google Scholar

Volterra, A. and Meldolesi, J. (2005). Astrocytes, from brain glue to communication elements: the revolution continues. Nat. Rev. Neurosci. 6: 626–640, https://doi.org/10.1038/nrn1722.Suche in Google Scholar PubMed

Wang, W., Putra, A., Schools, G.P., Ma, B., Chen, H., Kaczmarek, L.K., Barhanin, J., Lesage, F., and Zhou, M. (2013). The contribution of TWIK-1 channels to astrocyte K+ current is limited by retention in intracellular compartments. Front. Cell. Neurosci. 7: 246, doi:https://doi.org/10.3389/fncel.2013.00246.Suche in Google Scholar PubMed PubMed Central

Wagner, D.C., Scheibe, J., Glocke, I., Weise, G., Deten, A., Boltze, J., and Kranz, A. (2013). Object-based analysis of astroglial reaction and astrocyte subtype morphology after ischemic brain injury. Acta Neurobiol. Exp. 73: 79–87.10.55782/ane-2013-1923Suche in Google Scholar

Wang, M., Song, J., Xiao, W., Yang, L., Yuan, J., Wang, W., Yu, Z., and Xie, M. (2012). Changes in lipid-sensitive two-pore domain potassium channel TREK-1 expression and its involvement in astrogliosis following cerebral ischemia in rats. J. Mol. Neurosci. 46: 384–392, doi:https://doi.org/10.1007/s12031-011-9598-z.Suche in Google Scholar PubMed

Wei, T., Wang, Y., Xu, W., Liu, Y., Chen, H., and Yu, Z. (2019). KCa3.1 deficiency attenuates neuroinflammation by regulating an astrocyte phenotype switch involving the PI3K/AKT/GSK3β pathway. Neurobiol. Dis. 132: 104588, https://doi.org/10.1016/j.nbd.2019.104588.Suche in Google Scholar PubMed

Weller, J., Steinhäuser, C., and Seifert, G. (2016). pH-sensitive K+ currents and properties of K2P channels in murine hippocampal astrocytes. Adv. Protein Chem. Struct. Biol. 103: 263–294, https://doi.org/10.1016/bs.apcsb.2015.10.005.Suche in Google Scholar PubMed

Wheeler, M.A., Clark, I.C., Tjon, E.C., Li, Z., Zandee, S.E.J., Couturier, C.P., Watson, B.R., Scalisi, G., Alkwai, S., Rothhammer, V., et al. (2020). MAFG-driven astrocytes promote CNS inflammation. Nature 578: 593–599, doi:https://doi.org/10.1038/s41586-020-1999-0.Suche in Google Scholar PubMed PubMed Central

Williams, A., Piaton, G., and Lubetzki, C. (2007). Astrocytes-friends or foes in multiple sclerosis? Glia 55: 1300–1312, https://doi.org/10.1002/glia.20546.Suche in Google Scholar PubMed

Woo, D.H., Bae, J.Y., Nam, M.-H., An, H., Ju, Y.H., Won, J., Choi, J.H., Hwang, E.M., Han, K.-S., Bae, Y.C., et al. (2018). Activation of astrocytic μ-opioid receptor elicits fast glutamate release through TREK-1-containing K2P channel in hippocampal astrocytes. Front. Cell. Neurosci. 12: 319, doi:https://doi.org/10.3389/fncel.2018.00319.Suche in Google Scholar PubMed PubMed Central

Woo, D.H., Han, K.-S., Shim, J.W., Yoon, B.-E., Kim, E., Bae, J.Y., Oh, S.-J.J., Hwang, E.M., Mamorstein, A.D., Bae, Y.C., et al. (2012). TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation. Cell 151: 25–40, doi:https://doi.org/10.1016/j.cell.2012.09.005.Suche in Google Scholar PubMed

Wu, X., Liu, Y., Chen, X., Sun, Q., Tang, R., Wang, W., Yu, Z., and Xie, M. (2013). Involvement of TREK-1 activity in astrocyte function and neuroprotection under simulated ischemia conditions. J. Mol. Neurosci. 49: 499–506, doi:https://doi.org/10.1007/s12031-012-9875-5.Suche in Google Scholar PubMed

Yang, X.L., Wang, X., Shao, L., Jiang, G.T., Min, J.W., Mei, X.-Y.Y., He, X.-H.H., Liu, W.-H.H., Huang, W.-X.X., and Peng, B.-W.W. (2019). TRPV1 mediates astrocyte activation and interleukin-1β release induced by hypoxic ischemia (HI). J. Neuroinflammation 16: 114, doi:https://doi.org/10.1186/s12974-019-1487-3.Suche in Google Scholar PubMed PubMed Central

Yi, M., Wei, T., Wang, Y., Lu, Q., Chen, G., Gao, X., Geller, H.M., Chen, H., and Yu, Z. (2017). The potassium channel KCa3.1 constitutes a pharmacological target for astrogliosis associated with ischemia stroke. J. Neuroinflammation 14: 203, doi:https://doi.org/10.1186/s12974-017-0973-8.Suche in Google Scholar PubMed PubMed Central

Yun, S.P., Kam, T.I., Panicker, N., Kim, S., Oh, Y., Park, J.S., Kwon, S.H., Park, Y.J., Karuppagounder, S.S., Park, H., et al. (2018). Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease. Nat. Med. 24: 931–938, doi:https://doi.org/10.1038/s41591-018-0051-5.Suche in Google Scholar PubMed PubMed Central

Zamanian, J.L.J., Xu, L., Foo, L.C.L.L.C., Nouri, N., Zhou, L., Giffard, R.G., and Barres, B.A. (2012). Genomic analysis of reactive astrogliosis. J. Neurosci. 32: 6391–6410, doi:https://doi.org/10.1523/jneurosci.6221-11.2012.Suche in Google Scholar PubMed PubMed Central

Zamora, N.N., Cheli, V.T., Santiago González, D.A., Wan, R., and Paez, P.M. (2020). Deletion of voltage-gated calcium channels in astrocytes during demyelination reduces brain inflammation and promotes myelin regeneration in mice. J. Neurosci. 40: 3332–3347, https://doi.org/10.1523/jneurosci.1644-19.2020.Suche in Google Scholar PubMed PubMed Central

Zhang, Y. and Barres, B.A. (2010). Astrocyte heterogeneity: an underappreciated topic in neurobiology. Curr. Opin. Neurobiol. 20: 588–594, https://doi.org/10.1016/j.conb.2010.06.005.Suche in Google Scholar PubMed

Zhong, C.J., Chen, M.M., Lu, M., Ding, J.H., Du, R.H., and Hu, G. (2019). Astrocyte-specific deletion of Kir6.1/K-ATP channel aggravates cerebral ischemia/reperfusion injury through endoplasmic reticulum stress in mice. Exp. Neurol. 311: 225–233, https://doi.org/10.1016/j.expneurol.2018.10.005.Suche in Google Scholar PubMed

Zorec, R., Araque, A., Carmignoto, G., Haydon, P.G., Verkhratsky, A., and Parpura, V. (2012). Astroglial excitability and gliotransmission: an appraisal of Ca2+ as a signalling route. ASN Neuro 4: 103–119, https://doi.org/10.1042/AN20110061.Suche in Google Scholar PubMed PubMed Central

Received: 2021-05-10
Accepted: 2021-08-13
Published Online: 2021-08-30
Published in Print: 2021-11-25

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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