Presynaptic depolarization and calcium channel opening (Homo sapiens)

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12cytosolCACFD1 CACNA2D2(19-1150) Voltage Gated Ca2+ChannelCACNG4 CACNG2 Ca2+CACNA1E CACNB4 CACNA1A CACFD1 dimerCACNA2D3 CACNB3 CACNA1B Ca2+CACNA2D1(1-?) K+CACNB1 CACNB2


Action potentials are used in neurons to conduct signals along the axon and occur in electrically excitable cells like neurons and cardiac muscle cells. The action potentials travel in a wave along the membrane causing the voltage sensitive channels to open to allow influx of Na+ thereby causing the conduction of the signal along the axon. The resting membrane potential of cells including neurons is -70mv. An action potential is generated by a change in the membrane potential from -70mv to +40mv when voltage gated ion channels open altering membrane permeability to Na+ and K+.

The action potential travels down the axon and reaches the pre-synaptic terminal depolarizing the membrane in the pre-synaptic terminal. The depolarization causes the voltage-gated Ca2+ channels to open allowing the influx of Ca2+ that signals the release of neurotransmitter into the synaptic cleft.

View original pathway at:Reactome.


Pathway is converted from Reactome ID: 112308
Reactome version: 66
Reactome Author 
Reactome Author: Mahajan, SS

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Ontology Terms



  1. Yao CK, Lin YQ, Ly CV, Ohyama T, Haueter CM, Moiseenkova-Bell VY, Wensel TG, Bellen HJ.; ''A synaptic vesicle-associated Ca2+ channel promotes endocytosis and couples exocytosis to endocytosis.''; PubMed Europe PMC
  2. Diriong S, Lory P, Williams ME, Ellis SB, Harpold MM, Taviaux S.; ''Chromosomal localization of the human genes for alpha 1A, alpha 1B, and alpha 1E voltage-dependent Ca2+ channel subunits.''; PubMed Europe PMC


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101240view11:13, 1 November 2018ReactomeTeamreactome version 66
100779view20:40, 31 October 2018ReactomeTeamreactome version 65
100322view19:17, 31 October 2018ReactomeTeamreactome version 64
99867view16:00, 31 October 2018ReactomeTeamreactome version 63
99424view14:36, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99107view12:39, 31 October 2018ReactomeTeamreactome version 62
94505view09:21, 14 September 2017Mkutmonreactome version 61
86351view09:15, 11 July 2016ReactomeTeamreactome version 56
83053view09:47, 18 November 2015ReactomeTeamVersion54
81360view12:53, 21 August 2015ReactomeTeamVersion53
76829view08:05, 17 July 2014ReactomeTeamFixed remaining interactions
76533view11:50, 16 July 2014ReactomeTeamFixed remaining interactions
75866view09:51, 11 June 2014ReactomeTeamRe-fixing comment source
75566view10:36, 10 June 2014ReactomeTeamReactome 48 Update
74921view13:44, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74565view08:36, 30 April 2014ReactomeTeamReactome46
68994view17:44, 8 July 2013MaintBotUpdated to 2013 gpml schema
45188view10:00, 7 October 2011MartijnVanIerselOntology Term : 'neuron-to-neuron signaling pathways' added !
42023view21:51, 4 March 2011MaintBotAutomatic update
39826view05:51, 21 January 2011MaintBotNew pathway

External references


View all...
NameTypeDatabase referenceComment
CACFD1 ProteinQ9UGQ2 (Uniprot-TrEMBL)
CACFD1 dimerComplexR-HSA-5672066 (Reactome)
CACNA1A ProteinO00555 (Uniprot-TrEMBL)
CACNA1B ProteinQ00975 (Uniprot-TrEMBL)
CACNA1E ProteinQ15878 (Uniprot-TrEMBL)
CACNA2D1(1-?) ProteinQ9UIU0 (Uniprot-TrEMBL)
CACNA2D2(19-1150) ProteinQ9NY47 (Uniprot-TrEMBL)
CACNA2D3 ProteinQ8IZS8 (Uniprot-TrEMBL)
CACNB1 ProteinQ02641 (Uniprot-TrEMBL)
CACNB2 ProteinQ08289 (Uniprot-TrEMBL)
CACNB3 ProteinP54284 (Uniprot-TrEMBL)
CACNB4 ProteinO00305 (Uniprot-TrEMBL)
CACNG2 ProteinQ9Y698 (Uniprot-TrEMBL)
CACNG4 ProteinQ9UBN1 (Uniprot-TrEMBL)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
K+MetaboliteCHEBI:29103 (ChEBI)
Voltage Gated Ca2+ ChannelComplexR-HSA-210378 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
CACFD1 dimermim-catalysisR-HSA-5263618 (Reactome)
Ca2+ArrowR-HSA-210420 (Reactome)
Ca2+ArrowR-HSA-5263618 (Reactome)
Ca2+R-HSA-210420 (Reactome)
Ca2+R-HSA-5263618 (Reactome)
K+TBarR-HSA-210420 (Reactome)
R-HSA-210420 (Reactome) Ca2+ influx from the extracellular space into the presynaptic neuron through the Voltage Gated Ca2+ Channels (VGCC), is dependant on the arrival of an action potential at the synaptic bulb. The vesicle fusion and subsequent release of glutamate into the synapse is triggered by this influx of Ca2+. The VGCCs involved here could be of the N, P/Q or R type.

Hyperpolarization of the cell membrane due to KIR3 potassium channel activity inhibits this influx of Ca2+.

R-HSA-5263618 (Reactome) In drosophila, the calcium channel flower (fwe) is a homomultimeric protein on the plasma membrane of cells that couples synaptic exocytosis with endocytosis, both processes being regulated by Ca2+. Influx of Ca2+, triggered by voltage-gated Ca2+ channels, is necessary for synaptic vesicle fusion with the plasma membrane. Drosophila fwe is able to mediate Ca2+ influx and thus regulate synaptic endocytosis. Fwe can form at least a dimer but also higher multimers (Yao et al. 2009). The function of human calcium channel flower homologue (CACFD1) is based on inference from functional drosophila fwe.
Voltage Gated Ca2+ Channelmim-catalysisR-HSA-210420 (Reactome)
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