Paper Name |
Astrocytic Kir4.1 channels and gap junctions account for spontaneous epileptic seizure |
Author |
Mengmeng Du, Jiajia Li, Liang Chen, Yuguo Yu, Ying Wu |
Publication/Completion Time |
2018-03-28 |
Magazine Name |
Plos Computational Biology |
Vol |
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Related articles |
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Paper description |
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 con-
sisting of a single compartment neuron and 4 surrounding connected astrocytes and includ-
ing 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 astro-
cyte-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 con-
ductance and gap junction strength induce spontaneous epileptic activity in the absence of
external stimuli. |