Effect of GABAa-receptors on neuronal discharge and ion activity in focal seizures

Author:

Li Xin12,Qu Zhongjie12,Li Zipeng12,Su Rui3,Yin Bowen4,Yin Liyong4

Affiliation:

1. Yanshan University School of Electrical Engineering, , Qinhuangdao, Hebei 066004, P.R. China

2. Measurement Technology and Instrumentation Key Lab of Hebei Province , Qinhuangdao, Hebei 066004, P.R. China

3. Hebei Medical University School of Medical Imaging, , Shijiazhuang, Hebei 050011, P.R. China

4. Department of Neurology, The First Hospital of Qinhuangdao , Qinhuangdao, Hebei 066000, P.R. China

Abstract

Abstract Focal seizures are a type of epileptic event that has plagued the medical community for a long time, and the existing drug treatment is mainly based on the modulation of ${GABA}_a$-receptors to affect GABAergic signaling to achieve the therapeutic purpose. The majority of research currently focuses on the impact of ${GABA}_a$-receptors on neuronal firing, failing to analyze the molecular and ionic mechanisms involved. Specifically, the research on deeper-level mechanisms on how ${GABA}_a$-receptors affect neuronal firing by altering ion activity has not been addressed. This research aimed to study the effects of different ${GABA}_a$-receptor structures on ion activity in focal seizures model by adjusting parameters of the ${GABA}_a$-receptors: the rise time constant (${tau}_1$) and decay time constant (${tau}_2$). The research indicates that as the values of ${tau}_1$ and ${tau}_2$ of the ${GABA}_a$-receptor change, the ion concentration will vary based on the change of the ${GABA}_a$-receptor potential. To a certain extent, the duration of epileptic activity will also be affected to a certain extent. In conclusion, the alteration of ${GABA}_a$-receptor structure will affect the inhibitory effect of interneurons on pyramidal neurons, and different parameters of the ${GABA}_a$-receptor will directly impact the therapeutic effect.

Funder

Science Research Project of Hebei Education Department

First Hospital of Qinhuangdao

Medical-Industrial Crossover Special Incubation Project of Yanshan University

Hebei Natural Science Foundation

S&T Program of Hebei

Publisher

Oxford University Press (OUP)

Reference25 articles.

1. Inhibition, oscillations and focal seizures: an overview inspired by some historical notes;Avoli;Neurobiol Dis,2019

2. GABAA signaling, focal epileptiform synchronization and epileptogenesis;Avoli;Front Neural Circuits,2022

3. Initiation, propagation, and termination of partial (focal) seizures;Curtis;Cold Spring Harb Perspect Med,2015

4. GABAergic networks jump-start focal seizures;Curtis;Epilepsia,2016

5. Reevaluating the mechanisms of focal ictogenesis: the role of low-voltage fast activity;Curtis;Epilepsia,2009

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