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Ligand-gated ion channels (LGICs), also referred to as ionotropic receptors or channel-linked receptors, are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger (i.e., a ligand), such as a neurotransmitter.
The binding site of endogenous ligands on LGICs protein complexes are normally located on a different portion of the protein (an allosteric binding site) compared to where the ion conduction pore is located. The direct link between ligand binding and opening or closing of the ion channel, which is characteristic of ligand-gated ion channels, is contrasted with the indirect function of metabotropic receptors, which use second messengers. Ligand-gated ion channels are also different from voltage-gated ion channels (which open and close depending on membrane potential), and stretch-activated ion channels (which open and close depending on mechanical deformation of the cell membrane).
Regulation[edit | edit source]
The ion channel is regulated by a ligand and is usually very selective to one or more ions like Na+, K+, Ca2+, or Cl-. Such receptors located at synapses convert the chemical signal of presynaptically released neurotransmitter directly and very quickly into a postsynaptic electrical signal.
Structure[edit | edit source]
Each subunit of the pentameric channels consist of the extracellular ligand-binding domain and a transmembrane domain. Each transmembrane domain in the pentamer includes four transmembrane helixes.
Example: nicotinic acetylcholine receptor[edit | edit source]
The prototypic ligand-gated ion channel is the nicotinic acetylcholine receptor. It consists of a pentamer of protein subunits, with two binding sites for acetylcholine, which, when bound, alter the receptor's configuration and cause an internal pore to open. This pore allows Na+ ions to flow down their electrochemical gradient into the cell. With a sufficient number of channels opening at once, the intracellular Na+ concentration rises to the point at which the positive charge within the cell is enough to depolarize the membrane, and an action potential is initiated.
Classification[edit | edit source]
Many important ion channels are ligand-gated, and they show a significant degree of homology at the genetic level. LGICs are classified into three superfamilies:
Cys-loop receptors[edit | edit source]
The cys-loop receptors contain a characteristic loop formed by a disulfide bond between two cysteine residues and are subdivided into the type of ion that the corresponding channel conducts (anionic or cationic) and further into families defined by the endogenous ligand. They are usually pentameric.
protein name 
|CAE2, ECA2, GEFSP3|
protein name 
|ACHRA, ACHRD, CHRNA, CMS2A, FCCMS, SCCMS|
|CMS2A, SCCMS, ACHRB, CHRNB, CMS1D|
|delta||δ||CHRND||ACHRD, CMS2A, FCCMS, SCCMS|
|epsilon||ε||CHRNE||ACHRE, CMS1D, CMS1E, CMS2A, FCCMS, SCCMS|
|Zinc-activated ion channel
|ZAC||ZACN||ZAC1, L2m LGICZ, LGICZ1|
Ionotropic glutamate receptors[edit | edit source]
protein name 
|GLUA1, GluR1, GluRA, GluR-A, GluR-K1, HBGR1|
GLUA2, GluR2, GluRB, GluR-B, GluR-K2, HBGR2
GLUA3, GluR3, GluRC, GluR-C, GluR-K3
GLUA4, GluR4, GluRD, GluR-D
|GLUK5, GluR5, GluR-5, EAA3|
GLUK6, GluR6, GluR-6, EAA4
GLUK7, GluR7, GluR-7, EAA5
GLUK1, KA1, KA-1, EAA1
GLUK2, KA2, KA-2, EAA2
|GLUN1, NMDA-R1, NR1, GluRξ1|
|GLUN2A, NMDA-R2A, NR2A, GluRε1|
GLUN2B, NMDA-R2B, NR2B, hNR3, GluRε2
GLUN2C, NMDA-R2C, NR2C, GluRε3
GLUN2D, NMDA-R2D, NR2D, GluRε4
|GLUN3A, NMDA-R3A, NMDAR-L, chi-1|
ATP-gated channels[edit | edit source]
protein name 
Clinical relevance[edit | edit source]
Ligand-gated ion channels are likely to be the major site at which anaesthetic agents and ethanol have their effects, although unequivocal evidence of this is yet to be established. In particular, the GABA and NMDA receptors are affected by anaesthetic agents at concentrations similar to those used in clinical anaesthesia.
See also[edit | edit source]
References[edit | edit source]
- Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White (2008). Neuroscience. 4th ed., 156–7, Sinauer Associates.
- Connolly CN, Wafford KA (2004). The Cys-loop superfamily of ligand-gated ion channels: the impact of receptor structure on function. Biochem. Soc. Trans. 32 (Pt3): 529–34.
- Cascio M (2004). Structure and function of the glycine receptor and related nicotinicoid receptors. J. Biol. Chem. 279 (19): 19383–6.
- Collingridge GL, Olsen RW, Peters J, Spedding M (2008). A nomenclature for ligand-gated ion channels.. Neuropharmacology Epub ahead of print.
- A">Olsen RW, Sieghart W (2008). International Union of Pharmacology. LXX. Subtypes of γ-aminobutyric acidA receptors: classification on the basis of subunit composition, pharmacology, and function. Update.. Pharmacol. Rev. 60: 243-60.
- Krasowski MD, Harrison NL (1999). General anaesthetic actions on ligand-gated ion channels. Cell. Mol. Life Sci. 55 (10): 1278–303.
- Dilger JP (2002). The effects of general anaesthetics on ligand-gated ion channels. Br J Anaesth 89 (1): 41–51.
- Harris RA, Mihic SJ, Dildy-Mayfield JE, Machu TK (1995). Actions of anesthetics on ligand-gated ion channels: role of receptor subunit composition. FASEB J. 9 (14): 1454–62.
[edit | edit source]
- Revised Recommendations for Nomenclature of Ligand-Gated Ion Channels. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- Ligand-Gated Ion Channel database at European Bioinformatics Institute. Verified availability April 11, 2007.
Further reading[edit | edit source]
- Collingridge GL, Olsen RW, Peters J, Spedding M (2008). A nomenclature for ligand-gated ion channels. Neuropharmacology Epub ahead of print.
Membrane transport protein: ion channels
|Ca||Voltage-dependent calcium channel (L-type/CACNA1C, N-type, P-type, Q-type, R-type, T-type) - Inositol triphosphate receptor - Ryanodine receptor - Cation channels of sperm|
|Na: Sodium channel||Nav1.4 - Nav1.5 - Nav1.7 - Epithelial sodium channel|
|K: Potassium channel||Voltage-gated (KvLQT1, KvLQT2, KvLQT3, HERG, Shaker gene, KCNE1) - Calcium-activated (BK channel, SK channel) - Inward-rectifier (ROMK, KCNJ2) - Tandem pore domain|
|Cl: Chloride channel||Cystic fibrosis transmembrane conductance regulator|
|Porin||Aquaporin (1, 2, 3, 4)|
|Transient receptor potential||TRPA - TRPC (TRPC6) - TRPM (TRPM6) - TRPML (Mucolipin-1) - TRPP - TRPV (TRPV1, TRPV6)|
|Other/general||Gap junction - Stretch-activated ion channel - Ligand-gated ion channel - Voltage-gated ion channel - Cyclic nucleotide-gated ion channel - Two-pore channel|
Ion channel, receptor: ligand-gated ion channels
5-HT receptor (5-HT3 serotonin receptor (A)) - GABA receptor (GABA A (α1, α2, α3, α4, α5, α6, β1, β2, β3, γ2, γ3, ε), GABA C (ρ1, ρ2)) - Glycine receptor (α1, α2, β) - Nicotinic acetylcholine receptor (α1, α2, α3, α4, α5, α7, α9, β1, β2, β3, β4, δ, ε, (α4)2(β2)3, (α7)5, Ganglion type, Muscle type)
|Ionotropic glutamate receptors|
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