Ligand-gated ion channel: Difference between revisions

Neurotransmitter-gated ion-channel ligand binding domain
Neurotransmitter-gated ion-channel ligand binding domain
Identifiers
Symbol	Neur_chan_LBD
Pfam	PF02931
InterPro	IPR006202
PROSITE	PDOC00209
SCOP2	1lxg / SCOPe / SUPFAM
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	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

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	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 transmembrane region
Neurotransmitter-gated ion-channel transmembrane region
	Ligand-gated ion channel
Identifiers
Symbol	Neur_chan_memb
Pfam	PF02932
InterPro	IPR006029
PROSITE	PDOC00209
SCOP2	1cek / SCOPe / SUPFAM
TCDB	1.A.9
OPM superfamily	14
OPM protein	2bg9
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	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

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

The direct link to an 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. The Ligand-gated ion channels 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 engogenous ligand.

Anionic

Type	Class	IUPHAR-recommended protein name ^[5]	Gene	Previous names
GABA_A	alpha	α₁ α₂ α₃ α₄ α₅ α₆	GABRA1 GABRA2 GABRA3 GABRA4 GABRA5 GABRA6
	beta	β₁ β₂ β₃	GABRB1 GABRB2 GABRB3
	gamma	γ₁ γ₂ γ₃	GABRG1 GABRG2 GABRG3
	delta	δ	GABRD
	epsilon	ε	GABRE
	pi	π	GABRP
	theta	θ	GABRQ
	rho	ρ₁ ρ₂ ρ₃	GABRR1 GABRR2 GABRR3	GABA_C ^[6]
Glycine (GlyR)	alpha	α₁ α₂ α₃ α₄	GLRA1 GLRA2 GLRA3 GLRA4
Glycine (GlyR)	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-HT_3A 5-HT_3B 5-HT_3C 5-HT_3D 5-HT_3E
Nicotinic acetylcholine (nAChR)	alpha	α₁ α₂ α₃ α₄ α₅ α₆ α₇ α₉ α₁₀	CHRNA1 CHRNA2 CHRNA3 CHRNA4 CHRNA5 CHRNA6 CHRNA7 CHRNA9 CHRNA10
	beta	β₁ β₂ β₃ β₄	CHRNB1 CHRNB2 CHRNB3 CHRNB4
	gamma	γ	CHRNG
	delta	δ	CHRND
	epsilon	ε	CHRNE
Zinc-activated channel (ZAC)		ZAC	ZACN

Ionotropic glutamate receptors

The glutamate receptors bind the neurotransmitter glutamate:

Type	Class	IUPHAR-recommended protein name ^[5]	Gene	Previous names
AMPA	GluA	GluA1 GluA2 GluA3 GluA4	GRIA1 GRIA2 GRIA3 GRIA4	GLU_A1, GluR1, GluRA, GluR-A, GluR-K1, HBGR1 GLU_A2, GluR2, GluRB, GluR-B, GluR-K2, HBGR2 GLU_A3, GluR3, GluRC, GluR-C, GluR-K3 GLU_A4, GluR4, GluRD, GluR-D
Kainate	GluK	GluK1 GluK2 GluK3 GluK4 GluK5	GRIK1 GRIK2 GRIK3 GRIK4 GRIK5	GLU_K5, GluR5, GluR-5, EAA3 GLU_K6, GluR6, GluR-6, EAA4 GLU_K7, GluR7, GluR-7, EAA5 GLU_K1, KA1, KA-1, EAA1 GLU_K2, KA2, KA-2, EAA2
NMDA	GluN	GluN1 NRL1A NRL1B	GRIN1 GRINL1A GRINL1B	GLU_N1, NMDA-R1, NR1, GluRξ1
		GluN2A GluN2B GluN2C GluN2D	GRIN2A GRIN2B GRIN2C GRIN2D	GLU_N2A, NMDA-R2A, NR2A, GluRε1 GLU_N2B, NMDA-R2B, NR2B, hNR3, GluRε2 GLU_N2C, NMDA-R2C, NR2C, GluRε3 GLU_N2D, NMDA-R2D, NR2D, GluRε4
		GluN3A GluN3B	GRIN3A GRIN3B	GLU_N3A, NMDA-R3A, NMDAR-L, chi-1 GLU_3B, NMDA-R3B

ATP-gated channels

ATP-gated channels open in response to binding the nucleotide ATP:

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]

References

^ "ligand-gated channel" at Dorland's Medical Dictionary
^ ^a ^b Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White (2008). Neuroscience. 4th ed. Sinauer Associates. pp. 156–7. ISBN 978-0-87893-697-7.{{cite book}}: CS1 maint: multiple names: authors list (link)
^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ ^a ^b ^c ^d Collingridge GL, Olsen RW, Peters J, Spedding M (2008). "A nomenclature for ligand-gated ion channels". Neuropharmacology. Epub ahead of print. doi:10.1016/j.neuropharm.2008.06.063. PMID 18655795.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ A">Olsen RW, Sieghart W (2008). "International Union of Pharmacology. LXX. Subtypes of γ-aminobutyric acid_A receptors: classification on the basis of subunit composition, pharmacology, and function. Update". Pharmacol. Rev. 60: 243–60. PMID 18790874.
^ 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" (abstract). FASEB J. 9 (14): 1454–62. PMID 7589987.{{cite journal}}: CS1 maint: multiple names: authors list (link)

External links

"Revised Recommendations for Nomenclature of Ligand-Gated Ion Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
Ligand-Gated Ion Channel database at European Bioinformatics Institute. Verified availability April 11, 2007.

@@ Line 68: / Line 68: @@
 === 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 [[engogenous]] ligand.
+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 engogenous ligand.
 '''Anionic'''