Pathways & interactions
Glutamate-Gated Chloride Channel (IPR015680)
Short name: Glu_Cl_Channel
Overlapping homologous superfamilies
- Neurotransmitter-gated ion-channel (IPR006201)
- Glutamate-Gated Chloride Channel (IPR015680)
Neurotransmitter ligand-gated ion channels are transmembrane receptor-ion channel complexes that open transiently upon binding of specific ligands, allowing rapid transmission of signals at chemical synapses [PMID: 1721053, PMID: 1846404]. Five of these ion channel receptor families have been shown to form a sequence-related superfamily:
- Nicotinic acetylcholine receptor (AchR), an excitatory cation channel in vertebrates and invertebrates; in vertebrate motor endplates it is composed of alpha, beta, gamma and delta/epsilon subunits; in neurons it is composed of alpha and non-alpha (or beta) subunits [PMID: 18446614].
- Glycine receptor, an inhibitory chloride ion channel composed of alpha and beta subunits [PMID: 15383648].
- Gamma-aminobutyric acid (GABA) receptor, an inhibitory chloride ion channel; at least four types of subunits (alpha, beta, gamma and delta) are known [PMID: 18760291].
- Serotonin 5HT3 receptor, of which there are seven major types (5HT3-5HT7) [PMID: 10026168].
- Glutamate receptor, an excitatory cation channel of which at least three types have been described (kainate, N-methyl-D-aspartate (NMDA) and quisqualate) [PMID: 15165736].
These receptors possess a pentameric structure (made up of varying subunits), surrounding a central pore. All known sequences of subunits from neurotransmitter-gated ion-channels are structurally related. They are composed of a large extracellular glycosylated N-terminal ligand-binding domain, followed by three hydrophobic transmembrane regions which form the ionic channel, followed by an intracellular region of variable length. A fourth hydrophobic region is found at the C-terminal of the sequence [PMID: 1721053, PMID: 1846404].
Glutamate is classically thought to be a stimulatory neurotransmitter, however, studies in invertebrates have proven that glutamate also functions as an inhibitory ligand. The bulk of studies conducted in vivo have been on insects and crustaceans, where glutamate was first postulated to act on H-receptors resulting in a hyperpolarizing response to glutamate. Glutamate-gated chloride channels have been cloned from several nematodes and Drosophila [PMID: 9051935].