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

Cereb Cortex. 2024 Mar 1;34(3):bhae110. doi: 10.1093/cercor/bhae110.

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.

Keywords: GABAa-receptors; focal seizures; neuronal discharges; tau1; tau2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epilepsy*
  • Humans
  • Neurons / physiology
  • Patient Discharge*
  • Receptors, GABA-A / physiology
  • Seizures
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Receptors, GABA-A
  • gamma-Aminobutyric Acid