Pentameric ligand-gated ion channel (pLGIC) (pLGIC)

Pentameric ligand-gated ion channels (pLGICs), also known as Cys-loop receptors in eukaryotes, are a superfamily of transmembrane proteins that mediate fast chemical neurotransmission (Corringer et al., 2012, J Biol Chem). These channels are composed of five subunits arranged around a central ion-conducting pore, which opens in response to the binding of specific neurotransmitters such as acetylcholine, GABA, glycine, or serotonin (Hilf & Dutzler, 2008, Nature). The Gloeobacter violaceus ligand-gated ion channel (GLIC) is a prominent prokaryotic member of this family that has served as a vital structural model for understanding the molecular mechanisms of gating and allosteric modulation (Bocquet et al., 2009, Nature). In humans, pLGICs are critical for maintaining the balance between excitatory and inhibitory signals in the brain, and their dysfunction is linked to disorders such as epilepsy, Alzheimer's disease, and schizophrenia (Changeux & Christopoulos, 2016, Nat Rev Drug Discov). They are the primary targets for a wide range of clinically important drugs, including general anesthetics, benzodiazepines, and anti-emetics, which act by modulating the channel's open-state probability (Nury et al., 2011, Nature). Recent research continues to leverage GLIC and other homologs to design more selective therapies that target specific conformational states of these receptors (Sauguet et al., 2014, Nat Commun).

Other names

Cys-loop receptorPro-loop receptorGloeobacter violaceus ligand-gated ion channelGLICLigand-gated ion channel superfamilyELICErwinia chrysanthemi ligand-gated ion channel

Drugs targeting these channels typically act as agonists, antagonists, or allosteric modulators to either enhance or inhibit the flow of ions (such as Na+, K+, Ca2+, or Cl-) across the cell membrane, thereby altering neuronal excitability (Changeux & Christopoulos, 2016, Nat Rev Drug Discov). For instance, benzodiazepines act as positive allosteric modulators of GABA_A receptors to increase inhibitory tone, while varenicline acts as a partial agonist at nicotinic receptors to aid in smoking cessation (Sigel & Steinmann, 2012, J Biol Chem).