α1

Nomenclature: α1

Family: Nicotinic acetylcholine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 482 2q24-q32 CHRNA1 cholinergic receptor, nicotinic, alpha 1 (muscle) 7
Mouse 4 457 2 C3 Chrna1 cholinergic receptor, nicotinic, alpha polypeptide 1 (muscle) 5
Rat 4 457 3q23 Chrna1 cholinergic receptor, nicotinic, alpha 1 (muscle) 8
Previous and Unofficial Names
Muscle-type, muscle
CHRNA
acetylcholine receptor, nicotinic, alpha 1 (muscle)
cholinergic receptor, nicotinic, alpha polypeptide 1 (muscle)
acetylcholine receptor subunit alpha
cholinergic receptor nicotinic alpha polypeptide 1
cholinergic receptor nicotinic alpha polypeptide 1 (muscle)
cholinergic receptor, nicotinic, alpha polypeptide 1
Achr-1
Acra
AI385656
AI608266
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Functional Characteristics
(α1)2βγδ: PCa/PNa = 0.16 - 0.2, Pf = 2.1 – 2.9%; (α1)2βδε: PCa/PNa = 0.65 – 1.38, Pf = 4.1 – 7.2%
Natural/Endogenous Ligands
acetylcholine
Commonly used antagonists (Human)
(α1)2β1γδ and (α1)2β1δε: α-bungarotoxin > pancuronium > vecuronium > rocuronium > tubocurarine (IC50 = 43 - 82 nM)
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
succinylcholine Hs Full agonist - -
selective for (α1)2β1γδ
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
pancuronium Hs Antagonist - -
[125I]α-bungarotoxin Hs - - -
[3H]α-bungarotoxin Hs - - -
waglerin-1 Hs Antagonist - -
selective for (α1)2β1δε
α-bungarotoxin Hs Antagonist - -
α-conotoxin GI Hs Antagonist - -
α-conotoxin MI Hs Antagonist - -
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Use-dependent Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
gallamine Hs - no ~6.0 pIC50 - no
pIC50 ~6.0 (IC50 ~1x10-6 M) (α1)2β1γδ and (α1)2β1δε
Not voltage dependent
mecamylamine Hs - no ~5.82 pIC50 - no
pIC50 ~5.82 (IC50 ~1.5x10-6 M) (α1)2β1δε
Not voltage dependent
Tissue Distribution Comments
In vertebrates α1-subunit mRNA is generally expressed in skeletal muscle
Physiological Consequences of Altering Gene Expression
Homozygous knockout mice die at birth. Kyphosis and carpoptosis phenotypes are apparent in embryonic mice. Increased motor axon branching and expanded innervation were also seen. Spontaneous miniature and nerve-evoked endplate potentials were absent in muscle.
Species:  Mouse
Tissue:  in vivo
Technique:  Gene knockout
References:  1
Clinically-Relevant Mutations and Pathophysiology
Disease:  Myasthenia gravis
OMIM:  254200
Role: 
References:  4
Mutations not determined
Disease:  Congenital myasthenic syndromes due to low nAChR expression
References:  2-3
Click column headers to sort
Type Species Molecular location Description Reference
Frameshift Human Multiple locations
Missense Human Multiple locations
Disease:  Fetal akinesia deformation sequence disorders
References:  6
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human Multiple locations
Disease:  Slow-channel congenital myasthenic syndromes
OMIM:  601462
Orphanet:  98913
References:  2-3
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human Multiple locations
Disease:  Fast-channel congenital myasthenic syndromes
OMIM:  608930
Orphanet:  98913
References:  2-3
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human Multiple locations
Disease:  Multiple pterygium syndrome, lethal type
OMIM:  253290
Orphanet:  33108
References: 
Mutations not determined
General Comments
The human α1 subunit exists as two variants that arise from alternative splicing. The long variant is tabulated above.

References

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1. An MC, Lin W, Yang J, Dominguez B, Padgett D, Sugiura Y, Aryal P, Gould TW, Oppenheim RW, Hester ME et al.. (2010) Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms. Proc. Natl. Acad. Sci. U.S.A.107 (23): 10702-7. [PMID:20498043]

2. Engel AG, Ohno K, Sine SM. (2003) Sleuthing molecular targets for neurological diseases at the neuromuscular junction. Nat. Rev. Neurosci.4 (5): 339-52. [PMID:12728262]

3. Engel AG, Shen XM, Selcen D, Sine SM. (2010) What have we learned from the congenital myasthenic syndromes. J. Mol. Neurosci.40 (1-2): 143-53. [PMID:19688192]

4. Lindstrom JM. (2000) Acetylcholine receptors and myasthenia. Muscle Nerve23 (4): 453-77. [PMID:10716755]

5. Merlie JP, Sebbane R, Gardner S, Lindstrom J. (1983) cDNA clone for the alpha subunit of the acetylcholine receptor from the mouse muscle cell line BC3H-1. Proc. Natl. Acad. Sci. U.S.A.80 (12): 3845-9. [PMID:6344089]

6. Michalk A, Stricker S, Becker J, Rupps R, Pantzar T, Miertus J, Botta G, Naretto VG, Janetzki C, Yaqoob N et al.. (2008) Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders. Am. J. Hum. Genet.82 (2): 464-76. [PMID:18252226]

7. Noda M, Furutani Y, Takahashi H, Toyosato M, Tanabe T, Shimizu S, Kikyotani S, Kayano T, Hirose T, Inayama S. (1983) Cloning and sequence analysis of calf cDNA and human genomic DNA encoding alpha-subunit precursor of muscle acetylcholine receptor. Nature305 (5937): 818-23. [PMID:6688857]

8. Witzemann V, Stein E, Barg B, Konno T, Koenen M, Kues W, Criado M, Hofmann M, Sakmann B. (1990) Primary structure and functional expression of the alpha-, beta-, gamma-, delta- and epsilon-subunits of the acetylcholine receptor from rat muscle. Eur. J. Biochem.194 (2): 437-48. [PMID:1702709]

How to cite this page

Cecilia Gotti, Michael. J. Marks, Neil S. Millar, Susan Wonnacott.
Nicotinic acetylcholine receptors: α1. Last modified on 14/03/2014. Accessed on 23/07/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=462.