Acetylcholine binding and downstream events (Homo sapiens)

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1, 2, 5, 743446, 86, 8cytosolCHRNA5 CHRNA1 CHRNB2 CHRNE CHRNB3 CHRNA2 CHRNB4 CHRNB3 CHRND CHRNB4 CHRNA2 CHRNA5 CHRNA5 CHRNA7 Na+CHRNB3 CHRNG CHRNB4 CHRNA7 Highly calciumpermeable nicotinicacetylcholinereceptorsCa2+AcChoCHRNA1 CHRNB2 CHRNA4 CHRND CHRNB4 CHRNA9 CHRNE CHRNB2 CHRNA6 CHRNA4 CHRNA3 CHRNB4 CHRNA2 Highly sodiumpermeable nicotinicacetylcholinereceptorsCHRNB2 CHRNA1 CHRNB4 CHRNA3 CHRNA6 CHRNA4 CHRNA4 CHRNA2 CHRNA4 AcCho AcCho CHRNA9 CHRNB2 CHRNA6 CHRNA3 CHRNA6 0-acteylcholinebound to calciumpermeable nictonicacteylcholinereceptor complexO-acteylcholinebound to calciumpermeablepostsynapticnicotinicacetylcholinereceptorsCHRNA3 CHRNA3 CHRNG CHRNB2 O-Acetylcholinebound toAcetylcholinereceptorCHRNA5 CHRNB3 Highly calciumpermeablepostsynaptic nicotinicacetylcholinereceptorsNa+Ca2+AcCho CHRNA4 CHRNA3 CHRNA1


Description

Acetylcholine is the neurotransmitter found at neuromuscular junctions, synapses in the ganglia of the visceral motor system, and at a variety of sites within the central nervous system. A great deal is known about the function of cholinergic transmission at the neuromuscular junction and at ganglionic synapses, the actions of ACh in the central nervous system are not as well understood. Acetylcholine is synthesized in nerve terminals from acetyl coenzyme A (acetyl CoA) synthesized from glucose) and choline. This reaction is catalyzed by choline acetyltransferase (ChAT). The presence of acetyltransferase in a neuron is thus a strong indication that ACh is used as one of its transmitters. Choline is present in plasma at a concentration of about 10 mM, and is taken up into cholinergic neurons by a high affinity Na+/choline transporter. About 10,000 molecules of ACh are packaged into each neurotransmitter containing vesicle by a vesicular ACh transporter.

Nicotinic acetylcholine receptors (nAchR) are ionotropic receptors that can be activated by nicotine and permeable to of monovalent (sodium, potassium) and divalent cations(calcium), however, the permeability of sodium and/or calcium maybe high or low depending on the subunit composition of the receptor. Nicotinic acetylcholine receptors are expressed widely in the central and peripheral nervous system in the presynaptic terminal, terminal bouton and post synaptic neuron. Functionally nicotinic acetylcholine receptors in the pre synaptic and postsynaptic terminals behave similarly. Nicotinic AChR are a family of acetylcholine gated pentameric receptors that are formed by the association of various combinations of mostly alpha, beta subunits (for the neuronal type) and together with gamma, delta and epsilon subunits (for the muscle type). In addition, receptors may be more diverse due the fact that some receptors have same subunits but the stoichiometry of the subunits is different.

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Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 181431
Reactome-version 
Reactome version: 73
Reactome Author 
Reactome Author: Mahajan, SS

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Bibliography

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  1. Itier V, Bertrand D.; ''Neuronal nicotinic receptors: from protein structure to function.''; PubMed Europe PMC Scholia
  2. Grottick AJ, Trube G, Corrigall WA, Huwyler J, Malherbe P, Wyler R, Higgins GA.; ''Evidence that nicotinic alpha(7) receptors are not involved in the hyperlocomotor and rewarding effects of nicotine.''; PubMed Europe PMC Scholia
  3. Fucile S, Renzi M, Lax P, Eusebi F.; ''Fractional Ca(2+) current through human neuronal alpha7 nicotinic acetylcholine receptors.''; PubMed Europe PMC Scholia
  4. Gotti C, Clementi F, Fornari A, Gaimarri A, Guiducci S, Manfredi I, Moretti M, Pedrazzi P, Pucci L, Zoli M.; ''Structural and functional diversity of native brain neuronal nicotinic receptors.''; PubMed Europe PMC Scholia
  5. Albuquerque EX, Pereira EF, Alkondon M, Rogers SW.; ''Mammalian nicotinic acetylcholine receptors: from structure to function.''; PubMed Europe PMC Scholia
  6. Steinlein OK, Bertrand D.; ''Neuronal nicotinic acetylcholine receptors: from the genetic analysis to neurological diseases.''; PubMed Europe PMC Scholia
  7. Zouridakis M, Zisimopoulou P, Eliopoulos E, Poulas K, Tzartos SJ.; ''Design and expression of human alpha7 nicotinic acetylcholine receptor extracellular domain mutants with enhanced solubility and ligand-binding properties.''; PubMed Europe PMC Scholia
  8. Buisson B, Gopalakrishnan M, Arneric SP, Sullivan JP, Bertrand D.; ''Human alpha4beta2 neuronal nicotinic acetylcholine receptor in HEK 293 cells: A patch-clamp study.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114685view16:15, 25 January 2021ReactomeTeamReactome version 75
113059view10:58, 2 November 2020ReactomeTeamReactome version 74
112291view15:12, 9 October 2020ReactomeTeamReactome version 73
101672view13:50, 1 November 2018DeSlOntology Term : 'acetylcholine signaling pathway' added !
101655view11:51, 1 November 2018ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
0-acteylcholine

bound to calcium permeable nictonic acteylcholine

receptor complex
ComplexR-HSA-629600 (Reactome)
AcCho MetaboliteCHEBI:15355 (ChEBI)
AcChoMetaboliteCHEBI:15355 (ChEBI)
CHRNA1 ProteinP02708 (Uniprot-TrEMBL)
CHRNA2 ProteinQ15822 (Uniprot-TrEMBL)
CHRNA3 ProteinP32297 (Uniprot-TrEMBL)
CHRNA4 ProteinP43681 (Uniprot-TrEMBL)
CHRNA5 ProteinP30532 (Uniprot-TrEMBL)
CHRNA6 ProteinQ15825 (Uniprot-TrEMBL)
CHRNA7 ProteinP36544 (Uniprot-TrEMBL)
CHRNA9 ProteinQ9UGM1 (Uniprot-TrEMBL)
CHRNB2 ProteinP17787 (Uniprot-TrEMBL)
CHRNB3 ProteinQ05901 (Uniprot-TrEMBL)
CHRNB4 ProteinP30926 (Uniprot-TrEMBL)
CHRND ProteinQ07001 (Uniprot-TrEMBL)
CHRNE ProteinQ04844 (Uniprot-TrEMBL)
CHRNG ProteinP07510 (Uniprot-TrEMBL)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Highly calcium

permeable postsynaptic nicotinic acetylcholine

receptors
ComplexR-HSA-629581 (Reactome)
Highly calcium

permeable nicotinic acetylcholine

receptors
ComplexR-HSA-629586 (Reactome)
Highly sodium

permeable nicotinic acetylcholine

receptors
ComplexR-HSA-629576 (Reactome)
Na+MetaboliteCHEBI:29101 (ChEBI)
O-Acetylcholine

bound to Acetylcholine

receptor
ComplexR-HSA-629590 (Reactome)
O-acteylcholine

bound to calcium permeable postsynaptic nicotinic acetylcholine

receptors
ComplexR-HSA-629592 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
0-acteylcholine

bound to calcium permeable nictonic acteylcholine

receptor complex
ArrowR-HSA-629599 (Reactome)
0-acteylcholine

bound to calcium permeable nictonic acteylcholine

receptor complex
mim-catalysisR-HSA-622326 (Reactome)
AcChoR-HSA-629588 (Reactome)
AcChoR-HSA-629596 (Reactome)
AcChoR-HSA-629599 (Reactome)
Ca2+ArrowR-HSA-622326 (Reactome)
Ca2+ArrowR-HSA-629595 (Reactome)
Ca2+R-HSA-622326 (Reactome)
Ca2+R-HSA-629595 (Reactome)
Highly calcium

permeable postsynaptic nicotinic acetylcholine

receptors
R-HSA-629596 (Reactome)
Highly calcium

permeable nicotinic acetylcholine

receptors
R-HSA-629599 (Reactome)
Highly sodium

permeable nicotinic acetylcholine

receptors
R-HSA-629588 (Reactome)
Na+ArrowR-HSA-622325 (Reactome)
Na+R-HSA-622325 (Reactome)
O-Acetylcholine

bound to Acetylcholine

receptor
ArrowR-HSA-629588 (Reactome)
O-Acetylcholine

bound to Acetylcholine

receptor
mim-catalysisR-HSA-622325 (Reactome)
O-acteylcholine

bound to calcium permeable postsynaptic nicotinic acetylcholine

receptors
ArrowR-HSA-629596 (Reactome)
O-acteylcholine

bound to calcium permeable postsynaptic nicotinic acetylcholine

receptors
mim-catalysisR-HSA-629595 (Reactome)
R-HSA-622325 (Reactome) Nicotinic acetylcholine receptors containing aplha4(2) beta2 (3) and alpha3(2) beta4(3) are selectively highly Na+ permeable upon activation of these receptors by acetylcholine.
R-HSA-622326 (Reactome) Nicotinic acetylcholine receptors are activated upon ligand binding which opens the acetylcholine channels and permits Ca2+ and Na+ ion influx depending on the subunit composition and stoichiometry of the subunits. The ratio of Ca2+ to Na+ ion influx varies making the receptors either highly Na+ permeable or Ca2+ permeable.
R-HSA-629588 (Reactome) Nicotinic acetylcholine receptors bind two molecules of ligand, acetylcholine, in the alpha beta interface in receptors containing heteromeric subunits or in the interface of 2 aplha subunits in receptors containing homomeric subunits.
R-HSA-629595 (Reactome) Acetylcholine binding activates postsynaptic acetylchloine receptors that show Ca2+ currents which facilitate the process of long term potentiation (LTP).
R-HSA-629596 (Reactome) Nicotinic acetylcholine receptors bind two molecules of ligand, acetylcholine, in the alpha beta interface in receptors containing heteromeric subunits or in the interface of 2 aplha subunits in receptors containing homomeric subunits.
R-HSA-629599 (Reactome) Nicotinic acetylcholine receptors bind two molecules of ligand, acetylcholine, in the alpha beta interface in receptors containing heteromeric subunits or in the interface of 2 aplha subunits in receptors containing homomeric subunits.
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