IDEAS home Printed from https://ideas.repec.org/a/plo/pcbi00/1005877.html
   My bibliography  Save this article

Astrocytic Kir4.1 channels and gap junctions account for spontaneous epileptic seizure

Author

Listed:
  • Mengmeng Du
  • Jiajia Li
  • Liang Chen
  • Yuguo Yu
  • Ying Wu

Abstract

Experimental recordings in hippocampal slices indicate that astrocytic dysfunction may cause neuronal hyper-excitation or seizures. Considering that astrocytes play important roles in mediating local uptake and spatial buffering of K+ in the extracellular space of the cortical circuit, we constructed a novel model of an astrocyte-neuron network module consisting of a single compartment neuron and 4 surrounding connected astrocytes and including extracellular potassium dynamics. Next, we developed a new model function for the astrocyte gap junctions, connecting two astrocyte-neuron network modules. The function form and parameters of the gap junction were based on nonlinear regression fitting of a set of experimental data published in previous studies. Moreover, we have created numerical simulations using the above single astrocyte-neuron network module and the coupled astrocyte-neuron network modules. Our model validates previous experimental observations that both Kir4.1 channels and gap junctions play important roles in regulating the concentration of extracellular potassium. In addition, we also observe that changes in Kir4.1 channel conductance and gap junction strength induce spontaneous epileptic activity in the absence of external stimuli.Author summary: Astrocytes are critical regulators of normal physiological activity in the central nervous system, and one of their key functions is removing extracellular K+. In recent years, numerous biological studies have shown that astrocytic Kir4.1 channels and gap junctions between astrocytes act as major K+ clearance mechanisms. Dysfunction of either of these regulatory mechanisms may cause generation of K+-induced seizures. However, it is unclear how and to what extent these two K+-regulating processes lead to spontaneous epileptic activity. These questions were addressed in the present study by constructing novel single astrocyte-neuron network models and a coupled astrocyte-neuron module network connected by an astrocyte gap junction based on existing experimental observations and previous theoretical reports. Simulation results first verified that either down-regulation of astrocytic Kir4.1 channels or a decrease of the gap junction strength between astrocytes causes neuropathological hyper-excitability and spontaneous epileptic activity. These results imply that dysfunctional astrocytes should be considered as targets for therapeutic strategies in epilepsy.

Suggested Citation

  • Mengmeng Du & Jiajia Li & Liang Chen & Yuguo Yu & Ying Wu, 2018. "Astrocytic Kir4.1 channels and gap junctions account for spontaneous epileptic seizure," PLOS Computational Biology, Public Library of Science, vol. 14(3), pages 1-19, March.
  • Handle: RePEc:plo:pcbi00:1005877
    DOI: 10.1371/journal.pcbi.1005877
    as

    Download full text from publisher

    File URL: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005877
    Download Restriction: no

    File URL: https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1005877&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pcbi.1005877?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Ghanim Ullah & Steven J Schiff, 2010. "Assimilating Seizure Dynamics," PLOS Computational Biology, Public Library of Science, vol. 6(5), pages 1-12, May.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Junli Zhao & Jinyi Sun & Yang Zheng & Yanrong Zheng & Yuying Shao & Yulan Li & Fan Fei & Cenglin Xu & Xiuxiu Liu & Shuang Wang & Yeping Ruan & Jinggen Liu & Shumin Duan & Zhong Chen & Yi Wang, 2022. "Activated astrocytes attenuate neocortical seizures in rodent models through driving Na+-K+-ATPase," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Ouyang, Zhicheng & Yu, Yangyang & Liu, Zhilong & Feng, PeiHua, 2023. "Transition of spatiotemporal patterns in neuron–astrocyte networks," Chaos, Solitons & Fractals, Elsevier, vol. 169(C).
    3. Zhao, Jinyi & Yu, Ying & Wang, Qingyun, 2022. "Dynamical regulation of epileptiform discharges caused by abnormal astrocyte function with optogenetic stimulation," Chaos, Solitons & Fractals, Elsevier, vol. 164(C).
    4. Li, Jiajia & Zhang, Xuan & Du, Mengmeng & Wu, Ying, 2022. "Switching behavior of the gamma power in the neuronal network modulated by the astrocytes," Chaos, Solitons & Fractals, Elsevier, vol. 159(C).
    5. Shen, Zhuan & Zhang, Honghui & Du, Lin & Deng, Zichen & Kurths, Jürgen, 2023. "Initiation and termination of epilepsy induced by Lévy noise: A view from the cortical neural mass model," Chaos, Solitons & Fractals, Elsevier, vol. 167(C).

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Arthur, Joseph & Attarian, Adam & Hamilton, Franz & Tran, Hien, 2018. "Nonlinear Kalman filtering for censored observations," Applied Mathematics and Computation, Elsevier, vol. 316(C), pages 155-166.
    2. Madineh Sedigh-Sarvestani & Steven J Schiff & Bruce J Gluckman, 2012. "Reconstructing Mammalian Sleep Dynamics with Data Assimilation," PLOS Computational Biology, Public Library of Science, vol. 8(11), pages 1-15, November.
    3. Che, Yanqiu & Liu, Bei & Li, Huiyan & Lu, Meili & Wang, Jiang & Wei, Xile, 2017. "Robust stabilization control of bifurcations in Hodgkin-Huxley model with aid of unscented Kalman filter," Chaos, Solitons & Fractals, Elsevier, vol. 101(C), pages 92-99.
    4. Li, Jiajia & Wang, Rong & Du, Mengmeng & Tang, Jun & Wu, Ying, 2016. "Dynamic transition on the seizure-like neuronal activity by astrocytic calcium channel block," Chaos, Solitons & Fractals, Elsevier, vol. 91(C), pages 702-708.
    5. Shen, Zhuan & Zhang, Honghui & Du, Lin & Deng, Zichen & Kurths, Jürgen, 2023. "Initiation and termination of epilepsy induced by Lévy noise: A view from the cortical neural mass model," Chaos, Solitons & Fractals, Elsevier, vol. 167(C).
    6. Franz Hamilton & Alun L Lloyd & Kevin B Flores, 2017. "Hybrid modeling and prediction of dynamical systems," PLOS Computational Biology, Public Library of Science, vol. 13(7), pages 1-20, July.
    7. Li, Jiajia & Zhang, Xuan & Du, Mengmeng & Wu, Ying, 2022. "Switching behavior of the gamma power in the neuronal network modulated by the astrocytes," Chaos, Solitons & Fractals, Elsevier, vol. 159(C).

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pcbi00:1005877. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: ploscompbiol (email available below). General contact details of provider: https://journals.plos.org/ploscompbiol/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.