Abstract
GABAA receptors mediate most of the fast inhibitory transmission in the CNS. They form heteromeric complexes assembled from a large family of subunit genes. The existence of multiple GABAA receptor subtypes differing in subunit composition, localization and functional properties underlies their role for fine-tuning of neuronal circuits and genesis of network oscillations. The differential regulation of GABAA receptor subtypes represents a major facet of homeostatic synaptic plasticity and contributes to the excitation/inhibition (E/I) balance under physiological conditions and upon pathological challenges. The purpose of this review is to discuss recent findings highlighting the significance of GABAA receptor heterogeneity for the concept of E/I balance and its relevance for epilepsy. Specifically, we address the following issues: (1) role for tonic inhibition, mediated by extrasynaptic GABAA receptors, for controlling neuronal excitability; (2) significance of chloride ion transport for maintenance of the E/I balance in adult brain; and (3) molecular mechanisms underlying GABAA receptor regulation (trafficking, posttranslational modification, gene transcription) that are important for homoeostatic plasticity. Finally, the relevance of these findings is discussed in light of the involvement of GABAA receptors in epileptic disorders, based on recent experimental studies of temporal lobe epilepsy (TLE) and absence seizures and on the identification of mutations in GABAA receptor subunit genes underlying familial forms of epilepsy.
Highlights
The convulsant effects of GABA and glycine receptor antagonists, and the clinically relevant antiepileptic action of classical benzodiazepines, such as diazepam, led to the concept that epileptic seizures reflect an imbalance between excitatory and inhibitory transmission in the brain (Bradford, 1995; Gale, 1992; Olsen and Avoli, 1997)
We address the following issues: (1) role for tonic inhibition, mediated by extrasynaptic GABAA receptors, for controlling neuronal excitability; (2) significance of chloride ion transport for maintenance of the E/I balance in adult brain; and (3) molecular mechanisms underlying GABAA receptor regulation that are important for homoeostatic plasticity
We focus on three main factors underlying the contribution of GABA receptors for homeostatic synaptic plasticity (Mody, 2005)
Summary
The convulsant effects of GABA and glycine receptor antagonists, and the clinically relevant antiepileptic action of classical benzodiazepines, such as diazepam, led to the concept that epileptic seizures reflect an imbalance between excitatory and inhibitory transmission in the brain (Bradford, 1995; Gale, 1992; Olsen and Avoli, 1997). This view was further supported by the strong epileptogenic effects of glutamate receptor agonists, in particular kainic acid (Ben-Ari et al, 1980; Sperk, 1994). The classical dichotomy between inhibitory and excitatory GABAergic/glutamatergic transmission has to be revised and the role of GABAergic transmission in epilepsy is much more complex than suggested by simple pharmacological experiments
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
