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Acetylcholine (ACh) is a major neurotransmitter and neuromodulator that plays important roles in the central and peripheral nervous systems, the autonomic nervous system (ANS), and also in non-neuronal cells. In cholinergic neurons acetylcholine is synthetized from acetyl-CoA and choline by the choline O-acetyltransferase Chat. The glucose-derived pyruvate metabolism is the primary source of acetyl-CoA in the brain. Once synthesized, ACh is loaded into synaptic vesicles by the vesicular ACh tran

Pathway Diagram:

Elsevier Inc. cations ---> cation influx acetylcholine ---> released ACh muscle contraction cation influx Musk --+> NMJ nAChR glutamate presynaptic nAChRs --+> dopamine presynaptic nAChRs --+> glutamate presynaptic nAChRs --+> GABA presynaptic nAChRs --+> released ACh ACh hydrolysis, signal termination ---> choline Chat Ache Dok7 Musk postsynaptic nAChRs --+> post-synaptic modulation post-synaptic modulation cations ---> cation influx. cations cation influx. NMJ nAChR ---- Rapsn neurotransmitter release modulation Lrp4 ---- Musk Lrp4 dopaminergic neuron glutamatergic neuron GABAergic neuron cholinergic neuron choline ---> acetylcholine ACh hydrolysis, signal termination postsynaptic nAChRs ---- released ACh presynaptic nAChRs ---- released ACh Agrn ---- Lrp4 Agrn Dok7 ---- Musk Rapsn acetyl-CoA ---> acetylcholine NMJ nAChR ---- released ACh skeletal muscle fiber released ACh ---> ACh hydrolysis, signal termination Slc18a3 Slc5a7 NMJ nAChR postsynaptic nAChRs presynaptic nAChRs released ACh acetylcholine choline acetyl-CoA GABA dopamine NMJ nAChR --+> muscle contraction

Genes in Pathway:

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acetylcholine signaling pathway via nicotinic acetylcholine receptor term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Ache acetylcholinesterase JBrowse link 12 22,472,358 22,477,052 RGD:8549506
G Agrn agrin JBrowse link 5 173,589,910 173,622,813 RGD:8549508
G Chat choline O-acetyltransferase JBrowse link 16 8,576,858 8,686,131 RGD:8549504
G Chrna1 cholinergic receptor nicotinic alpha 1 subunit JBrowse link 3 60,445,657 60,460,724 RGD:8549508
G Chrna10 cholinergic receptor nicotinic alpha 10 subunit JBrowse link 1 167,206,722 167,212,199 RGD:8549510
G Chrna2 cholinergic receptor nicotinic alpha 2 subunit JBrowse link 15 42,808,897 42,825,179 RGD:8549510
G Chrna3 cholinergic receptor nicotinic alpha 3 subunit JBrowse link 8 59,594,007 59,607,122 RGD:8549510
G Chrna4 cholinergic receptor nicotinic alpha 4 subunit JBrowse link 3 176,533,182 176,547,965 RGD:8549510
G Chrna5 cholinergic receptor nicotinic alpha 5 subunit JBrowse link 8 59,561,817 59,590,172 RGD:8549510
G Chrna6 cholinergic receptor nicotinic alpha 6 subunit JBrowse link 16 68,860,018 68,866,718 RGD:8549510
G Chrna7 cholinergic receptor nicotinic alpha 7 subunit JBrowse link 1 123,897,341 124,039,263 RGD:8549510
G Chrna9 cholinergic receptor nicotinic alpha 9 subunit JBrowse link 14 43,883,450 43,890,171 RGD:8549510
G Chrnb1 cholinergic receptor nicotinic beta 1 subunit JBrowse link 10 56,390,671 56,403,255 RGD:8549508
G Chrnb2 cholinergic receptor nicotinic beta 2 subunit JBrowse link 2 189,088,570 189,096,785 RGD:8549510
G Chrnb3 cholinergic receptor nicotinic beta 3 subunit JBrowse link 16 68,876,442 68,913,628 RGD:8549510
G Chrnb4 cholinergic receptor nicotinic beta 4 subunit JBrowse link 8 59,610,489 59,629,073 RGD:8549510
G Chrnd cholinergic receptor nicotinic delta subunit JBrowse link 9 94,286,550 94,294,968 RGD:8549508
G Chrne cholinergic receptor nicotinic epsilon subunit JBrowse link 10 57,238,960 57,246,750 RGD:8549508
G Chrng cholinergic receptor nicotinic gamma subunit JBrowse link 9 94,302,218 94,308,591 RGD:8549508
G Dok7 docking protein 7 JBrowse link 14 80,925,409 80,963,454 RGD:8549508
G Lrp4 LDL receptor related protein 4 JBrowse link 3 80,362,643 80,416,684 RGD:8549508
G Musk muscle associated receptor tyrosine kinase JBrowse link 5 75,392,790 75,498,694 RGD:8549508
G Rapsn receptor-associated protein of the synapse JBrowse link 3 79,859,815 79,869,486 RGD:8549508
G Slc18a3 solute carrier family 18 member A3 JBrowse link 16 8,682,668 8,685,529 RGD:8549504
G Slc5a7 solute carrier family 5 member 7 JBrowse link 9 5,294,377 5,330,822 RGD:8549504

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Functional Classpresynaptic nAChRs
Functional ClassnAChR at the neuromuscular junction
Functional Classpostsynaptic nAChRs

Pathway Gene Annotations

Disease Annotations Associated with Genes in the acetylcholine signaling pathway via nicotinic acetylcholine receptor
Disease TermsGene Symbols
Abnormalities, MultipleChrna4
AlcoholismChrna3 , Chrna5
Alzheimer DiseaseAche , Chat , Chrna4 , Chrna7 , Chrnb2 , Slc18a3
Amphetamine-Related DisordersAche
Anxiety DisordersChrna5 , Chrnb2
AsthmaChat , Slc18a3 , Slc5a7
Attention Deficit Disorder with HyperactivityChrna4 , Chrnb2
Auditory Perceptual DisordersChrna7
Autism Spectrum DisorderChrna7
Autistic DisorderChrna4 , Chrna7 , Chrnb2
Autoimmune DiseasesRapsn
Autosomal Dominant Nocturnal Frontal Lobe EpilepsyChrna2 , Chrna4 , Chrnb2
Bone Diseases, DevelopmentalChrng
Brain InjuriesChrna7 , Slc18a3
Breast NeoplasmsAche
Carcinoma, Renal CellAche
Chromosome 15q13.3 Microdeletion SyndromeChrna7
congenital myasthenic syndrome 8Agrn
Congenital Myasthenic Syndrome IbAgrn , Dok7
Congenital Myasthenic Syndrome with Episodic ApneaChat
Developmental DisabilitiesChrna4
Diabetes Mellitus, ExperimentalAche
Diabetes Mellitus, Type 1Ache
Drug-Related Side Effects and Adverse ReactionsAche
EndotoxemiaAche , Slc18a3
Epilepsy, Frontal LobeChrna4 , Chrnb2
Epilepsy, GeneralizedChrna7
Epilepsy, Nocturnal Frontal Lobe, Type 1Chrna4
Epilepsy, Nocturnal Frontal Lobe, Type 3Chrnb2
Epilepsy, Nocturnal Frontal Lobe, Type 4Chrna2
Genetic Diseases, InbornChrna4
Glaucoma, Angle-ClosureChat
Growth DisordersAche
Heart FailureChrna4
Hernia, UmbilicalChrna7
Hirschsprung DiseaseAche
Huntington DiseaseAche , Chat , Slc18a3
Hydrops FetalisChrna1
Idiopathic Basal Ganglia Calcification 1Chrna6 , Chrnb3
InflammationChrna4 , Chrnb2
Learning DisordersAche
Leukemia, Myeloid, AcuteAgrn
Lewy Body DiseaseChrna4 , Chrna7
Liver Cirrhosis, ExperimentalAche
Lung NeoplasmsChrna2 , Chrna3 , Chrna5 , Chrna7 , Chrnb4
Memory DisordersAche , Chrna7
Meningitis, BacterialAche
Movement DisordersAche
Multiple Pterygium SyndromeChrna1 , Chrnd , Chrng
Multiple pterygium syndrome, lethal typeChrna1 , Chrnd , Chrng
Multiple SclerosisAche
muscle tissue diseaseRapsn
Muscle WeaknessChrnd
Muscular DiseasesRapsn
Muscular DystrophiesAche
Myasthenia GravisAche , Musk
Myasthenia Gravis, Autoimmune, ExperimentalChrna1 , Musk
Myasthenia, Familial Infantile, 1Chrne , Rapsn
Myasthenic syndrome, congenital, 17Lrp4
Myasthenic Syndrome, Congenital, Fast-ChannelChrna1 , Chrnd , Chrne
Myasthenic Syndrome, Congenital, IeRapsn
Myasthenic Syndrome, Congenital, Postsynaptic Slow-ChannelChrna1 , Chrnb1 , Chrnd , Chrne
Myasthenic Syndrome, Congenital, Type IdChrnb1 , Chrne , Musk , Rapsn
Myasthenic Syndrome, Congenital, with Facial Dysmorphism, associated with Acetylcholine Receptor DeficiencyChrnb1 , Chrnd , Musk , Rapsn
Myasthenic Syndrome, Congenital, with Pre- and Postsynaptic DefectsAgrn
Myasthenic Syndromes, CongenitalAgrn , Chat , Chrna1 , Chrnb1 , Chrnd , Chrne , Chrng , Dok7 , Lrp4 , Musk , Rapsn , Slc18a3 , Slc5a7
Neoplasm InvasivenessChrna7
Nerve DegenerationChrna7 , Chrnb2
Nervous System DiseasesAche , Chrna4
Neurobehavioral ManifestationsChrna7
Neuropathy, Distal Hereditary Motor, Type VIIASlc5a7
Organophosphate PoisoningAche
Parkinson DiseaseAche
Pena Shokeir Syndrome, Type 1Dok7 , Musk , Rapsn
Peripheral Nervous System DiseasesChrng
Pleomorphic Xanthoastrocytoma Ache
Prenatal InjuriesAche
prostate cancerSlc5a7
Prostatic NeoplasmsAche , Slc5a7
Reflex, AbnormalChrnb2
Reperfusion InjuryChat
Respiratory InsufficiencyMusk
Retinal DiseasesChat
Sclerosteosis 2Lrp4
SeizuresAche , Chat , Chrna2 , Chrna3 , Chrna4 , Chrna5 , Chrna7 , Chrnb2 , Chrnb4
Sleep Wake DisordersChrna4 , Chrnb2
Spina Bifida CysticaChrna7
Status EpilepticusSlc18a3
Stress Disorders, TraumaticAche
Substance Withdrawal SyndromeChrna5 , Chrna6 , Chrna7 , Chrnb2 , Chrnb4
Substance-Related DisordersChrna5
Sudden Infant DeathChrna7 , Chrnb2
Syndactyly Cenani Lenz TypeLrp4
Tobacco Addiction, Susceptibility ToChrna3 , Chrna4 , Chrna5 , Chrna6 , Chrnb3
Tobacco Use DisorderChrna3 , Chrna4 , Chrna5 , Chrna7
Tooth AbnormalitiesLrp4
Transplant RejectionSlc5a7
Urinary Bladder DiseasesSlc18a3
Pathway Annotations Associated with Genes in the acetylcholine signaling pathway via nicotinic acetylcholine receptor
Pathway TermsGene Symbols
acetylcholine metabolic pathwayAche , Chat
acetylcholine signaling pathway via muscarinic acetylcholine receptorAche , Chat , Slc18a3 , Slc5a7
acetylcholine signaling pathway via nicotinic acetylcholine receptorAche , Agrn , Chat , Chrna1 , Chrna10 , Chrna2 , Chrna3 , Chrna4 , Chrna5 , Chrna6 , Chrna7 , Chrna9 , Chrnb1 , Chrnb2 , Chrnb3 , Chrnb4 , Chrnd , Chrne , Chrng , Dok7 , Lrp4 , Musk , Rapsn , Slc18a3 , Slc5a7
alfentanil pharmacodynamics pathwayChrna4 , Chrnb2
bupivacaine pharmacodynamics pathwayChrna4 , Chrnb2
buprenorphine pharmacodynamics pathwayChrna4 , Chrnb2
calcium/calcium-mediated signaling pathwayChrna7
cell-extracellular matrix signaling pathwayAgrn
chloroprocaine pharmacodynamics pathwayChrna4 , Chrnb2
citalopram pharmacodynamics pathwayChrna4 , Chrnb2
cocaine pharmacodynamics pathwayChrna4 , Chrnb2
codeine and morphine pharmacodynamics pathwayChrna4 , Chrnb2
desipramine pharmacodynamics pathwayChrna4 , Chrnb2
diphenoxylate pharmacodynamics pathwayChrna4 , Chrnb2
escitalopram pharmacodynamics pathwayChrna4 , Chrnb2
ethylmorphine pharmacodynamics pathwayChrna4 , Chrnb2
fentanyl pharmacodynamics pathwayChrna4 , Chrnb2
fluoxetine pharmacodynamics pathwayChrna4 , Chrnb2
glycerophospholipid metabolic pathwayAche , Chat
heroin pharmacodynamics pathwayChrna4 , Chrnb2
hydrocodone pharmacodynamics pathwayChrna4 , Chrnb2
hydromorphone pharmacodynamics pathwayChrna4 , Chrnb2
imipramine pharmacodynamics pathwayChrna4 , Chrnb2
levacetylmethadol pharmacodynamics pathwayChrna4 , Chrnb2
levobupivacaine phgarmacodynamics pathwayChrna4 , Chrnb2
levorphanol pharmacodynamics pathwayChrna4 , Chrnb2
lidocaine pharmacodynamics pathwayChrna4 , Chrnb2
mepivacaine pharmacodynamics pathwayChrna4 , Chrnb2
methadone pharmacodynamics pathwayChrna4 , Chrnb2
nalbuphine pharmacodynamics pathwayChrna4 , Chrnb2
naloxone pharmacodynamics pathwayChrna4 , Chrnb2
naltrexone pharmacodynamics pathwayChrna4 , Chrnb2
nicotine pharmacodynamics pathwayChrna3 , Chrna4 , Chrnb2
nicotine pharmacokinetics pathwayChrna3 , Chrna4 , Chrnb2
organophosphate response pathwayAche
oxybuprocaine pharmacodynamics pathwayChrna4 , Chrnb2
oxycodone pharmacodynamics pathwayChrna4 , Chrnb2
oxymorphone pharmacodynamics pathwayChrna4 , Chrnb2
pentazocine pharmacodynamics pathwayChrna4 , Chrnb2
prilocaine pharmacodynamics pathwayChrna4 , Chrnb2
procaine pharmacodynamics pathwayChrna4 , Chrnb2
remifentanil pharmacodynamics pathwayChrna4 , Chrnb2
ropivacaine pharmacodynamics pathwayChrna4 , Chrnb2
tramadol pharmacodynamics pathwayChrna4 , Chrnb2

References Associated with the acetylcholine signaling pathway via nicotinic acetylcholine receptor:

Ontology Path Diagram:

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Import into Pathway Studio: