KEGG   PATHWAY: ko04725Help
Entry
ko04725                     Pathway                                

Name
Cholinergic synapse
Description
Acetylcholine (ACh) is a neurotransmitter widely distributed in the central (and also peripheral, autonomic and enteric) nervous system (CNS). In the CNS, ACh facilitates many functions, such as learning, memory, attention and motor control. When released in the synaptic cleft, ACh binds to two distinct types of receptors: Ionotropic nicotinic acetylcholine receptors (nAChR) and metabotropic muscarinic acetylcholine receptors (mAChRs). The activation of nAChR by ACh leads to the rapid influx of Na+ and Ca2+ and subsequent cellular depolarization. Activation of mAChRs is relatively slow (milliseconds to seconds) and, depending on the subtypes present (M1-M5), they directly alter cellular homeostasis of phospholipase C, inositol trisphosphate, cAMP, and free calcium. In the cleft, ACh may also be hydrolyzed by acetylcholinesterase (AChE) into choline and acetate. The choline derived from ACh hydrolysis is recovered by a presynaptic high-affinity choline transporter (CHT).
Class
Organismal Systems; Nervous system
BRITE hierarchy
Pathway map
Cholinergic synapse
ko04725

All organismsOrtholog table
Disease
H00215  
Periodic paralysis
H00606  
Early infantile epileptic encephalopathy
H00746  
Hypokalemic periodic paralysis (HypoPP)
H00748  
Andersen-Tawil syndrome (ATS)
H00749  
Episodic ataxias
H00770  
Congenital myasthenic syndrome
H00775  
Familial or sporadic hemiplegic migraine
H00806  
Benign familial neonatal and infantile epilepsies
H00807  
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)
Drug
D00805  
Metrifonate (USP/INN)
D03791  
Dichlorvos (USAN/INN)
Other DBs
BSID: 
GO: 
Orthology
K00623  
choline O-acetyltransferase [EC:2.3.1.6]
K01049  
acetylcholinesterase [EC:3.1.1.7]
K14636  
MFS transporter, DHA1 family, solute carrier family 18 (vesicular acetylcholine transporter), member 3
K04129  
muscarinic acetylcholine receptor M1
K04131  
muscarinic acetylcholine receptor M3
K04133  
muscarinic acetylcholine receptor M5
K04634  
guanine nucleotide-binding protein G(q) subunit alpha
K04635  
guanine nucleotide-binding protein subunit alpha-11
K05858  
phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K04958  
inositol 1,4,5-triphosphate receptor type 1
K04959  
inositol 1,4,5-triphosphate receptor type 2
K04960  
inositol 1,4,5-triphosphate receptor type 3
K02677  
classical protein kinase C [EC:2.7.11.13]
K04926  
potassium voltage-gated channel KQT-like subfamily member 1
K04927  
potassium voltage-gated channel KQT-like subfamily member 2
K04928  
potassium voltage-gated channel KQT-like subfamily member 3
K04929  
potassium voltage-gated channel KQT-like subfamily member 4
K04930  
potassium voltage-gated channel KQT-like subfamily member 5
K04996  
potassium inwardly-rectifying channel subfamily J member 2
K05005  
potassium inwardly-rectifying channel subfamily J member 12
K04998  
potassium inwardly-rectifying channel subfamily J member 4
K05007  
potassium inwardly-rectifying channel subfamily J member 14
K04130  
muscarinic acetylcholine receptor M2
K04132  
muscarinic acetylcholine receptor M4
K04630  
guanine nucleotide-binding protein G(i) subunit alpha
K04534  
guanine nucleotide-binding protein G(o) subunit alpha
K04536  
guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537  
guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K07825  
guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K04538  
guanine nucleotide-binding protein subunit beta-4
K04539  
guanine nucleotide-binding protein subunit beta-5
K07826  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K04540  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04347  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04547  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548  
guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K04997  
potassium inwardly-rectifying channel subfamily J member 3
K05000  
potassium inwardly-rectifying channel subfamily J member 6
K02833  
GTPase HRas
K07827  
GTPase KRas
K07828  
GTPase NRas
K04368  
mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04371  
mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04379  
proto-oncogene protein c-fos
K04809  
nicotinic acetylcholine receptor alpha-7
K04806  
nicotinic acetylcholine receptor alpha-4
K04813  
nicotinic acetylcholine receptor beta-2
K04805  
nicotinic acetylcholine receptor alpha-3
K04815  
nicotinic acetylcholine receptor beta-4
K04808  
nicotinic acetylcholine receptor alpha-6
K08041  
adenylate cyclase 1 [EC:4.6.1.1]
K08042  
adenylate cyclase 2 [EC:4.6.1.1]
K08043  
adenylate cyclase 3 [EC:4.6.1.1]
K08044  
adenylate cyclase 4 [EC:4.6.1.1]
K08045  
adenylate cyclase 5 [EC:4.6.1.1]
K08046  
adenylate cyclase 6 [EC:4.6.1.1]
K08047  
adenylate cyclase 7 [EC:4.6.1.1]
K08048  
adenylate cyclase 8 [EC:4.6.1.1]
K08049  
adenylate cyclase 9 [EC:4.6.1.1]
K04345  
protein kinase A [EC:2.7.11.11]
K05870  
cyclic AMP-responsive element-binding protein 1
K04374  
cyclic AMP-dependent transcription factor ATF-4
K09048  
cyclic AMP-responsive element-binding protein 3
K09047  
cyclic AMP-responsive element-binding protein 5
K04515  
calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]
K05869  
calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17]
K04447  
Janus kinase 2 [EC:2.7.10.2]
K05703  
tyrosine-protein kinase Fyn [EC:2.7.10.2]
K00922  
phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153]
K02649  
phosphoinositide-3-kinase, regulatory subunit
K04456  
RAC serine/threonine-protein kinase [EC:2.7.11.1]
K02161  
apoptosis regulator BCL-2
K04344  
voltage-dependent calcium channel P/Q type alpha-1A
K04849  
voltage-dependent calcium channel N type alpha-1B
K04850  
voltage-dependent calcium channel L type alpha-1C
K04851  
voltage-dependent calcium channel L type alpha-1D
K04853  
voltage-dependent calcium channel L type alpha-1F
K04857  
voltage-dependent calcium channel L type alpha-1S
K14387  
solute carrier family 5 (high affinity choline transporter), member 7
Compound
C00010  
CoA
C00024  
Acetyl-CoA
C00033  
Acetate
C00076  
Calcium cation
C00114  
Choline
C00165  
Diacylglycerol
C00238  
Potassium cation
C00575  
3',5'-Cyclic AMP
C01245  
D-myo-Inositol 1,4,5-trisphosphate
C01330  
Sodium cation
C01996  
Acetylcholine
C04637  
1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
Reference
  Authors
Nestler EJ, Hyman SE, Malenka RC.
  Title
Molecular neuropharmacology: A foundation for clinical neuroscience
  Journal
The McGraw-Hill Companies, Inc. (2001)
Reference
  Authors
Nicholls JG, Martin AR, Wallace BG, Fuchs PA.
  Title
From neuron to brain, 4th ed.
  Journal
Sunderland, MA: Sinauer associates (2001)
Reference
  Authors
Dajas-Bailador F, Wonnacott S
  Title
Nicotinic acetylcholine receptors and the regulation of neuronal signalling.
  Journal
Trends Pharmacol Sci 25:317-24 (2004)
Reference
  Authors
Resende RR, Adhikari A
  Title
Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation.
  Journal
Cell Commun Signal 7:20 (2009)
Reference
  Authors
Origlia N, Kuczewski N, Pesavento E, Aztiria E, Domenici L
  Title
The role of cholinergic system in neuronal plasticity: focus on visual cortex and muscarinic receptors.
  Journal
Arch Ital Biol 146:165-88 (2008)
Reference
  Authors
Oldenburg IA, Ding JB
  Title
Cholinergic modulation of synaptic integration and dendritic excitability in the  striatum.
  Journal
Curr Opin Neurobiol 21:425-32 (2011)
Reference
  Authors
Lanzafame AA, Christopoulos A, Mitchelson F
  Title
Cellular signaling mechanisms for muscarinic acetylcholine receptors.
  Journal
Receptors Channels 9:241-60 (2003)
Reference
  Authors
Brown DA
  Title
Muscarinic acetylcholine receptors (mAChRs) in the nervous system: some functions and mechanisms.
  Journal
J Mol Neurosci 41:340-6 (2010)
Reference
  Authors
Chang KT, Berg DK
  Title
Voltage-gated channels block nicotinic regulation of CREB phosphorylation and gene expression in neurons.
  Journal
Neuron 32:855-65 (2001)
Reference
  Authors
Soreq H, Seidman S
  Title
Acetylcholinesterase--new roles for an old actor.
  Journal
Nat Rev Neurosci 2:294-302 (2001)
Reference
  Authors
Sharma G, Vijayaraghavan S
  Title
Nicotinic receptor signaling in nonexcitable cells.
  Journal
J Neurobiol 53:524-34 (2002)
Reference
  Authors
Araque A, Martin ED, Perea G, Arellano JI, Buno W
  Title
Synaptically released acetylcholine evokes Ca2+ elevations in astrocytes in hippocampal slices.
  Journal
J Neurosci 22:2443-50 (2002)
Reference
  Authors
Lucas-Meunier E, Fossier P, Baux G, Amar M
  Title
Cholinergic modulation of the cortical neuronal network.
  Journal
Pflugers Arch 446:17-29 (2003)
Reference
  Authors
Abreu-Villaca Y, Filgueiras CC, Manhaes AC
  Title
Developmental aspects of the cholinergic system.
  Journal
Behav Brain Res 221:367-78 (2011)

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