GABA and its receptors in epilepsy.
Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the mammalian brain. It acts through 2 classes of receptors, GABAA receptors that are ligand-operated ion channels and the G-protein-coupled metabotropic GABAB receptors. Impairment of GABAergic transmission by genetic mutations or application of GABA receptor antagonists induces epileptic seizures, whereas drugs augmenting GABAergic transmission are used for antiepileptic therapy. In animal epilepsy models and in tissue from patients with temporal lobe epilepsy, loss in subsets of hippocampal GABA neurons is observed. On the other hand, electrophysiological and neurochemical studies indicate a compensatory increase in GABAergic transmission at certain synapses. Also, at the level of the GABAA receptor, neurodegeneration-induced loss in receptors is accompanied by markedly altered expression of receptor subunits in the dentate gyrus and other parts of the hippocampal formation, indicating altered physiology and pharmacology of GABAA receptors. Such mechanisms may be highly relevant for seizure induction, augmentation of endogenous protective mechanisms, and resistance to antiepileptic drug therapy. Other studies suggest a role of GABAB receptors in absence seizures. Presynaptic GABAB receptors suppress neurotransmitter release. Depending on whether this action is exerted in GABAergic or glutamatergic neurons, there may be anticonvulsant or proconvulsant actions.
Sperk
Günther
G
Department of Pharmacology, University of Innsbruck, Austria.
Furtinger
Sabine
S
Schwarzer
Christoph
C
Pirker
Susanne
S
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D004827:Epilepsy / Q000503:physiopathology*; D006801:Humans; D018079:Receptors, GABA / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid