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Ligand-gated_ion_channel

Ligand-gated ion channel


Neurotransmitter-gated ion-channel transmembrane region
Identifiers
Symbol	Neur_chan_memb
Pfam	PF02932
InterPro	IPR006029
SCOP	1cek
TCDB	1.A.9
OPM family	14
OPM protein	2bg9
Available PDB structures: 1oedE:242-483 2bg9E:242-389 1dxzA:260-291 3mra :301-325 1a11 :276-298 1cekA:276-298 1eq8E:276-298 1motA:277-304 1vryA:281-337

Neurotransmitter-gated ion-channel ligand binding domain
Identifiers
Symbol	Neur_chan_LBD
Pfam	PF02931
InterPro	IPR006202
SCOP	1lxg
Available PDB structures: 1ux2F:34-142 1uw6D:34-142 1i9bE:34-142 1uv6J:34-142 1yi5A:34-142 2bysD:23-226 2byrI:23-226 2byqA:23-226 2br7D:23-226 2bypC:23-225 2bynA:23-226 2bg9B:28-241 1lk1G:28-241 1olkE:28-241 1ol8B:26-230 1ol3A:26-230 1ol4B:26-230 1kl8B:201-219 1kc4B:201-219 1ol9A:26-230 1y5tB:230-235 1l4wB:206-226 1ljzB:206-226 1idgB:205-222 1tos :91-99 1lxgB:205-222 1lxhB:205-222 1idhB:205-222 1tor :91-100 1oleA:39-245 1olfA:29-235 1oljC:29-235

The Ligand-gated ion channels, also referred to as LGICs, or ionotropic receptors, are a group of intrinsic transmembrane ion channels that are opened or closed in response to binding of a chemical messenger, as opposed to voltage-gated ion channels or stretch-activated ion channels.^[1]

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1 Regulation
2 Structure
3 Example: nicotinic acetylcholine receptor
4 Classification and examples
5 Clinical relevance
6 See also
7 References

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.^[2]

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, permeable to Na⁺, 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 and examples

Many important ion channels are ligand-gated, and they show a great degree of homology at the genetic level. The Ligand-gated ion channels are classified into three superfamilies:

The Cys-loop receptors

anionic
- GABA_A
  - α₁ (GABRA1), α₂ (GABRA2), α₃ (GABRA3), α₄ (GABRA4), α₅ (GABRA5), α₆ (GABRA6)
  - β₁ (GABRB1), β₂ (GABRB2), β₃ (GABRB3)
  - γ₁ (GABRG1), γ₂ (GABRG2), γ₃ (GABRG3)
  - δ (GABRD), ε (GABRE), π (GABRP), θ (GABRQ)
- GABA_C
  - ρ₁ (GABRR1), ρ₂ (GABRR2), ρ₃ (GABRR3)
- Glycine (GlyR)
  - GlyR-α₁ (GLRA1), GlyR-α₂ (GLRA2), GlyR-α₃ (GLRA3), GlyR-α₄ (GLRA4)
  - GlyR-β (GLRB)
cationic
- 5-HT₃ serotonin receptor
  - 5-HT_3A (HTR3A), 5-HT_3B (HTR3B), 5-HT_3C (HTR3C), 5-HT_3D (HTR3D), 5-HT_3E (HTR3E)
- nicotinic acetylcholine receptor (nAChR)
  - nAChR-α₁ (CHRNA1), nAChR-α₂ (CHRNA2), nAChR-α₃ (CHRNA3), nAChR-α₄ (CHRNA4), nAChR-α₅ (CHRNA5), nAChR-α₆ (CHRNA6), nAChR-α₇ (CHRNA7), nAChR-α₈ (CHRNA8), nAChR-α₉ (CHRNA9), nAChR-α₁₀ (CHRNA10)
  - nAChR-β₁ (CHRNB1), nAChR-β₂ (CHRNB2), nAChR-β₃ (CHRNB3), nAChR-β₄ (CHRNB4)
  - nAChR-δ (CHRND), nAChR-ε (CHRNE), nAChR-γ (CHRNG)

The ionotropic glutamate receptors

AMPA
- GluR₁ (GRIA1), GluR₂ (GRIA2), GluR₃ (GRIA3), GluR₄, alternatively called GluRA-D (GRIA4)
Kainate
- GluR₅ (GRIK1), GluR₆ (GRIK2), GluR₇ (GRIK3)
- KA₁ (GRIK4), KA₂ (GRIK5)
NMDA
- NR1 (GRIN1)
- NR2A (GRIN2A), NR2B (GRIN2B), NR2C (GRIN2C), NR2D (GRIN2D)

The ATP-gated channels

P2X
- P2X₁ (P2RX1), P2X₂ (P2RX2), P2X₃ (P2RX3), P2X₄ (P2RX4), P2X₅ (P2RX5), P2X₇ (P2RX7), P2X_L1 (P2RXL1)

Clinical relevance

Ligand-gated ion channels are likely to be the major site at which anaesthetic agents have their effects, although unequivocal evidence of this is yet to be established.^[3]^[4] In particular, the GABA and NMDA receptors are affected by anaesthetic agents at concentrations similar to those used in clinical anaesthesia.^[5]

References

^ 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. doi:10.1042/BST0320529. PMID 15157178.
^ Cascio M (2004). "Structure and function of the glycine receptor and related nicotinicoid receptors". J. Biol. Chem. 279 (19): 19383–6. doi:10.1074/jbc.R300035200. PMID 15023997.
^ Krasowski MD, Harrison NL (1999). "General anaesthetic actions on ligand-gated ion channels". Cell. Mol. Life Sci. 55 (10): 1278–303. doi:10.1007/s000180050371. PMID 10487207.
^ Dilger JP (2002). "The effects of general anaesthetics on ligand-gated ion channels". Br J Anaesth 89 (1): 41–51. doi:10.1093/bja/aef161. PMID 12173240.
^ 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. PMID 7589987.

v • d • e Membrane transport protein: ion channels
Ca²⁺: Calcium channel	Voltage-dependent calcium channel (L-type/Ca_vα(1.1, 1.2, 1.3, 1.4), N-type, P-type/Ca_vα(2.1), Q-type, R-type, T-type, β-subunits (β1, β2, β4), γ-subunits (γ2) • Inositol triphosphate receptor • Ryanodine receptor • Cation channels of sperm • Two-pore channel
Na⁺: Sodium channel	Na_vα (1.1, 1.2, 1.4, 1.5, 1.7, 1.9) • Na_vβ (1, 3, 4) • Epithelial sodium channel
K⁺: Potassium channel	Voltage-gated (K_vα (1.1, 1.2, 1.3, 1.4, 1.5, 2.1, 4.2, 4.3, 7.1, 7.2, 7.3, 7.4, 10.1, 11.1/hERG) • K_vβ (1, 2), Shaker gene, KCNE1) • Calcium-activated (BK channel, SK channel, SK3) • Inward-rectifier K_ir (1.1, 2.1, 2.2, 2.3, 3.1, 3.2, 3.4, 4.1, 4.2, 6.1, 6.2)) • Tandem pore domain K2P (1, 2, 3, 4, 6, 9)
Cl^-: Chloride channel	Cystic fibrosis transmembrane conductance regulator
Porin	Aquaporin (1, 2, 3, 4) • Voltage-dependent anion channel (1)
Cations: TRP	TRPA (1) • TRPC (1, 2, 3, 4, 4AP, 5, 6, 7) • TRPM (1, 2, 3, 4, 5, 6, 7, 8) • TRPML (Mucolipin-1) • TRPP (1, 2)• TRPV (1, 2, 3, 4, 5, 6)
Other/general	Voltage-gated ion channel • Ligand-gated ion channel • Cyclic nucleotide-gated ion channel (α1, α3, β3, H1, H2, H4) • Stretch-activated ion channel

v • d • e Ion channel, receptor: ligand-gated ion channels
Cys-loop receptors	5-HT receptor (5-HT₃ serotonin receptor (A)) - GABA receptor (GABA A (α₁, α₂, α₃, α₅, α₆, β₁, β₂, β₃, γ₂, ε), GABA C (ρ₁)) - Glycine receptor (α₁) - Nicotinic acetylcholine receptor (α1, α2, α3, α4, α5, α7, β2, β3, β4, δ, ε, (α4)₂(β2)₃, (α7)₅, Ganglion type, Muscle type)
Ionotropic glutamate receptors	AMPA (1, 2, 3, 4) - Kainate (1, 2) - NMDA (1, 2A, 2B, 2C, 2D)
ATP-gated channels	Purinergic receptors (P2X (1, 4, 5, 7))

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Ligand-gated_ion_channel". A list of authors is available in Wikipedia.