Gamma-aminobutyric acid type A receptor delta subunit-containing extrasynaptic receptor (delta-GABA_A receptor) (delta-GABA_A receptor)

Extrasynaptic GABA_A receptors containing the delta (δ) subunit are a distinct class of ligand-gated ion channels that mediate tonic inhibition in the central nervous system. Unlike synaptic GABA_A receptors that respond to bursts of GABA with rapid, phasic currents, these receptors are located outside the synapse and respond to low ambient concentrations of GABA, providing a persistent inhibitory tone that regulates overall neuronal excitability (Belelli et al., 2009). They are particularly sensitive to neurosteroids like allopregnanolone, which act as potent positive allosteric modulators, and are notably insensitive to benzodiazepines (Zheleznova et al., 2009). Dysregulation of these receptors is implicated in various neuropsychiatric conditions, including postpartum depression, epilepsy, and insomnia (Maguire & Mody, 2008). Therapeutic targeting of δ-containing receptors has led to the development of neurosteroid-based treatments such as brexanolone and zuranolone, which offer rapid-acting antidepressant effects (Meltzer-Brody et al., 2018). These receptors represent a critical target for modulating brain states and treating disorders characterized by GABAergic imbalance. They are also involved in the mechanism of action of certain anesthetics and analgesics (Klinger et al., 2012).

Other names

Delta-containing GABA_A receptorExtrasynaptic GABA_A receptorδ-GABA_ARGABRD-containing receptor

Positive allosteric modulation and direct agonism