What is the role of gamma-aminobutyric acid A (GABA-A) inhibition in the pathophysiology of epileptic seizures?

Updated: May 30, 2019
  • Author: David Y Ko, MD; Chief Editor: Selim R Benbadis, MD  more...
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Answer

Some epilepsies may involve mutations or lack of expression of the different GABA-A receptor complex subunits, the molecules that govern their assembly, or the molecules that modulate their electrical properties. For example, hippocampal pyramidal neurons may not be able to assemble alpha 5 beta 3 gamma 3 receptors because of deletion of chromosome 15 (ie, Angelman syndrome).

Changes in the distribution of subunits of the GABA-A receptor complex have been demonstrated in several animal models of focal-onset epilepsy, such as the electrical-kindling, chemical-kindling, and pilocarpine models. In the pilocarpine model, decreased concentrations of mRNA for the alpha 5 subunit of the surviving interneurons were observed in the CA1 region of the rat hippocampus. [7]


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