Psychology Wiki

Assessment | Biopsychology | Comparative | Cognitive | Developmental | Language | Individual differences | Personality | Philosophy | Social |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |

Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)


LGIC

Ligand-gated ion channel

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),[1] such as a neurotransmitter.[2]

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).[2][3]

Regulation[]

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.

Many LGICs are additionally modulated by allosteric ligands, by channel blockers, ions, or the membrane potential.

Structure[]

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.[4]

Example: nicotinic acetylcholine receptor[]

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[]

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[]

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.

Anionic

Type Class IUPHAR-recommended
protein name [5]
Gene Previous names
GABAA alpha α1
α2
α3
α4
α5
α6
GABRA1
GABRA2
GABRA3
GABRA4
GABRA5
GABRA6
EJM, ECA4
beta β1
β2
β3
GABRB1
GABRB2
GABRB3


ECA5
gamma γ1
γ2
γ3
GABRG1
GABRG2
GABRG3
CAE2, ECA2, GEFSP3
delta δ GABRD
epsilon ε GABRE
pi π GABRP
theta θ GABRQ
rho ρ1
ρ2
ρ3
GABRR1
GABRR2
GABRR3
GABAC[6]
Glycine
(GlyR)
alpha α1
α2
α3
α4
GLRA1
GLRA2
GLRA3
GLRA4
STHE

beta β GLRB

Cationic

Type Class IUPHAR-recommended
protein name [5]
Gene Previous names
Serotonin
(5-HT)
5-HT3 5-HT3A
5-HT3B
5-HT3C
5-HT3D
5-HT3E
HTR3A
HTR3B
HTR3C
HTR3D
HTR3E
5-HT3A
5-HT3B
5-HT3C
5-HT3D
5-HT3E
Nicotinic acetylcholine
(nAChR)
alpha α1
α2
α3
α4
α5
α6
α7
α9
α10
CHRNA1
CHRNA2
CHRNA3
CHRNA4
CHRNA5
CHRNA6
CHRNA7
CHRNA9
CHRNA10
ACHRA, ACHRD, CHRNA, CMS2A, FCCMS, SCCMS







beta β1
β2
β3
β4
CHRNB1
CHRNB2
CHRNB3
CHRNB4
CMS2A, SCCMS, ACHRB, CHRNB, CMS1D
EFNL3, nAChRB2

gamma γ CHRNG ACHRG
delta δ CHRND ACHRD, CMS2A, FCCMS, SCCMS
epsilon ε CHRNE ACHRE, CMS1D, CMS1E, CMS2A, FCCMS, SCCMS
Zinc-activated ion channel
(ZAC)
ZAC ZACN ZAC1, L2m LGICZ, LGICZ1

Ionotropic glutamate receptors[]

The glutamate receptors bind the neurotransmitter glutamate. They form tetramers.

Type Class IUPHAR-recommended
protein name [5]
Gene Previous names
AMPA GluA GluA1
GluA2
GluA3
GluA4
GRIA1
GRIA2
GRIA3
GRIA4
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
Kainate GluK GluK1
GluK2
GluK3
GluK4
GluK5
GRIK1
GRIK2
GRIK3
GRIK4
GRIK5
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
NMDA GluN GluN1
NRL1A
NRL1B
GRIN1
GRINL1A
GRINL1B
GLUN1, NMDA-R1, NR1, GluRξ1


GluN2A
GluN2B
GluN2C
GluN2D
GRIN2A
GRIN2B
GRIN2C
GRIN2D
GLUN2A, NMDA-R2A, NR2A, GluRε1
GLUN2B, NMDA-R2B, NR2B, hNR3, GluRε2
GLUN2C, NMDA-R2C, NR2C, GluRε3
GLUN2D, NMDA-R2D, NR2D, GluRε4
GluN3A
GluN3B
GRIN3A
GRIN3B
GLUN3A, NMDA-R3A, NMDAR-L, chi-1
GLU3B, NMDA-R3B

ATP-gated channels[]

ATP-gated channels open in response to binding the nucleotide ATP. They form trimers.

Type Class IUPHAR-recommended
protein name [5]
Gene Previous names
P2X N/A P2X1
P2X2
P2X3
P2X4
P2X5
P2X6
P2X7
P2RX1
P2RX2
P2RX3
P2RX4
P2RX5
P2RX6
P2RX7
P2X1
P2X2
P2X3
P2X4
P2X5
P2X6
P2X7

Clinical relevance[]

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.[7][8] In particular, the GABA and NMDA receptors are affected by anaesthetic agents at concentrations similar to those used in clinical anaesthesia.[9]

See also[]


References[]

  1. Template:DorlandsDict
  2. 2.0 2.1 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.
  3. 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.
  4. Cascio M (2004). Structure and function of the glycine receptor and related nicotinicoid receptors. J. Biol. Chem. 279 (19): 19383–6.
  5. 5.0 5.1 5.2 5.3 Collingridge GL, Olsen RW, Peters J, Spedding M (2008). A nomenclature for ligand-gated ion channels.. Neuropharmacology Epub ahead of print.
  6. 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.
  7. Krasowski MD, Harrison NL (1999). General anaesthetic actions on ligand-gated ion channels. Cell. Mol. Life Sci. 55 (10): 1278–303.
  8. Dilger JP (2002). The effects of general anaesthetics on ligand-gated ion channels. Br J Anaesth 89 (1): 41–51.
  9. 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.

External links[]

Further reading[]

  • Collingridge GL, Olsen RW, Peters J, Spedding M (2008). A nomenclature for ligand-gated ion channels. Neuropharmacology Epub ahead of print.



This page uses Creative Commons Licensed content from Wikipedia (view authors).