Pentameric ligand-gated ion channel (pLGIC)

Pentameric ligand-gated ion channels (pLGICs), also known as Cys-loop receptors in eukaryotes, are a superfamily of transmembrane proteins that play a fundamental role in fast synaptic transmission within the central and peripheral nervous systems (IUPHAR/BPS Guide to PHARMACOLOGY). These receptors are composed of five protein subunits arranged pseudosymmetrically around a central ion-conducting pore, which opens upon the binding of specific neurotransmitters such as acetylcholine, GABA, glycine, or serotonin (UniProt). By converting chemical signals into electrical impulses, pLGICs regulate neuronal excitability and are critical for processes including motor control, cognition, and sensory perception (StatPearls). Dysregulation of pLGIC function is implicated in a wide range of neurological and psychiatric disorders, including epilepsy, Alzheimer's disease, and anxiety (PubMed, PMID: 25103112). Consequently, they are major therapeutic targets for a variety of drugs, including anesthetics, sedatives, anti-emetics, and smoking cessation aids, which modulate channel activity through orthosteric or allosteric mechanisms (Nature Reviews Neuroscience, doi:10.1038/nrn.2017.90).

Other names

Cys-loop receptorLigand-gated ion channel superfamilyPro-loop receptorNicotinicoid receptor superfamily

Drugs targeting pLGICs typically act as orthosteric agonists or antagonists, or as allosteric modulators that enhance (PAMs) or inhibit (NAMs) the channel's response to its endogenous ligand, thereby regulating neuronal excitability and signal propagation (IUPHAR/BPS Guide to PHARMACOLOGY).