Electrophysiology of ionotropic GABA receptors

Abstract

GABAA receptors are ligand-gated chloride channels and ionotropic receptors of GABA, the main inhibitory neurotransmitter in vertebrates. In this review, we discuss the major and diverse roles GABAA receptors play in the regulation of neuronal communication and the functioning of the brain. GABAA receptors have complex electrophysiological properties that enable them to mediate different types of currents such as phasic and tonic inhibitory currents. Their activity is finely regulated by membrane voltage, phosphorylation and several ions. GABAA receptors are pentameric and are assembled from a diverse set of subunits. They are subdivided into numerous subtypes, which differ widely in expression patterns, distribution and electrical activity. Substantial variations in macroscopic neural behavior can emerge from minor differences in structure and molecular activity between subtypes. Therefore, the diversity of GABAA receptors widens the neuronal repertoire of responses to external signals and contributes to shaping the electrical activity of neurons and other cell types.

Significance of GABAA Receptor for Cognitive Function and Hippocampal Pathology

“…The nature of contextual fear learning-induced pre-and post-synaptic plasticity is complicated by the fact that learning also affects GABA A receptor-mediated inhibitory synapses in CA1 pyramidal neurons [9][10][11]. GABA A receptors typically consist of 2 α and 2 β subunits, together with either an γ or δ subunit [12]. Pore opening allows Cl − influx to induce postsynaptic hyperpolarization upon GABA binding.…”

Relating neurosteroid modulation of inhibitory neurotransmission to behaviour

“…Importantly, the GABA A R subunit family is diverse, grouped by sequence homology into the categories: α1‐6, β1‐3, γ1‐3, ρ1‐3, δ, ε, θ and π subunits. In the mammalian CNS, this subunit repertoire underpins the expression of approximately 20–30 native GABA A R isoforms 29–33 . The majority of GABA A Rs are composed of two α subunits, two β subunits and a γ subunit (predominantly, but not exclusively, the γ2 subunit).…”

Sex differences in GABAA receptor subunit transcript expression are mediated by genotype in subjects with alcohol‐related cirrhosis of the liver

“…of alternate splicing may be the regulation of subunit expression. 54 A heritable component is demonstrable with AUD, but the pattern is not clear. 55 Genome-wide Association Studies have highlighted the involvement of GABRs.…”

“…Variants occur in the 5′UTR and in introns, as well as coding regions. The main function of alternate splicing may be the regulation of subunit expression 54 …”