Page last updated: 2024-10-24

voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels

Definition

Target type: molecularfunction

Regulation of presynaptic cytosolic calcium ion concentrations via the action of voltage-gated calcium ion channels. [GOC:dos, PMID:15548655]

Voltage-gated calcium channels (VGCCs) are transmembrane proteins that play a crucial role in regulating presynaptic cytosolic calcium levels, which are essential for neurotransmitter release. These channels open in response to changes in membrane potential, allowing calcium ions to flow into the presynaptic terminal. This influx of calcium triggers a cascade of events that ultimately leads to the fusion of synaptic vesicles with the presynaptic membrane and the release of neurotransmitters into the synaptic cleft.

The molecular function of VGCCs in regulating presynaptic cytosolic calcium levels can be described in detail as follows:

1. **Voltage Sensing:** The VGCC protein contains a voltage sensor domain that is sensitive to changes in membrane potential. When the membrane depolarizes, the voltage sensor moves, causing a conformational change in the channel protein.

2. **Channel Opening:** This conformational change opens the channel pore, allowing calcium ions to flow down their electrochemical gradient from the extracellular space into the presynaptic terminal.

3. **Calcium Influx:** The influx of calcium ions increases the concentration of calcium in the presynaptic cytosol.

4. **Calcium Binding:** Calcium ions bind to specific proteins, such as synaptotagmin, which is a calcium sensor protein located on synaptic vesicles.

5. **Vesicle Fusion and Neurotransmitter Release:** Binding of calcium to synaptotagmin triggers the fusion of synaptic vesicles with the presynaptic membrane, releasing neurotransmitters into the synaptic cleft.

6. **Channel Closure:** Once the membrane potential returns to its resting state, the voltage sensor moves back to its original position, closing the channel pore and stopping the influx of calcium ions.

VGCCs are highly regulated, with their activity influenced by factors such as membrane potential, neurotransmitter receptors, and intracellular signaling pathways. This regulation ensures that neurotransmitter release is tightly controlled and occurs only when necessary.

Different types of VGCCs exist, each with distinct properties and roles in regulating presynaptic calcium levels and neurotransmitter release. These differences allow for fine-tuning of synaptic transmission based on the specific needs of the synapse.'
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Proteins (3)

ProteinDefinitionTaxonomy
Voltage-dependent L-type calcium channel subunit beta-2A voltage-dependent L-type calcium channel subunit beta-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q08289]Homo sapiens (human)
5-hydroxytryptamine receptor 1BA 5-hydroxytryptamine receptor 1B that is encoded in the genome of human. [PRO:WCB, UniProtKB:P28222]Homo sapiens (human)
Voltage-dependent L-type calcium channel subunit beta-4A voltage-dependent L-type calcium channel subunit beta-4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O00305]Homo sapiens (human)

Compounds (69)

CompoundDefinitionClassesRoles
tryptamineaminoalkylindole;
aralkylamino compound;
indole alkaloid;
tryptamines
human metabolite;
mouse metabolite;
plant metabolite
8-hydroxy-2-(di-n-propylamino)tetralin8-Hydroxy-2-(di-n-propylamino)tetralin: A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin.

8-OH-DPAT : A tetralin substituted at positions 1 and 7 by hydroxy and dipropylamino groups respectively
phenols;
tertiary amino compound;
tetralins
serotonergic antagonist
1-(1-naphthyl)piperazine1-(1-naphthyl)piperazine: serotonin agonist; structure given in first sourceN-arylpiperazine
5-(nonyloxy)tryptamine5-(nonyloxy)tryptamine: a 5-HT1D beta serotonin receptor agonist; structure given in first source

5-nonyloxytryptamine : A tryptamine derivative that consists of serotonin bearing an additional O-nonyl substituent. 5-HT1B selective agonist, several times more potent than sumatriptan and inactive as a 5-HT1A agonist (Ki at 5-HT1B = 1 nM, selectivity over 5-HT1A > 300-fold).
aromatic ether;
primary amino compound;
tryptamines
serotonergic agonist
5-carboxamidotryptamine5-carboxamidotryptamine: agonist of 5-HT receptor; structure given in first sourcetryptamines
methylbufotenin5-methoxy-N,N-dimethyltryptamine : A tryptamine alkaloid that is N,N-dimethyltryptamine substituted by a methoxy group at position 5.aromatic ether;
tertiary amino compound;
tryptamine alkaloid
hallucinogen;
plant metabolite
5-methoxytryptamine5-methoxytryptamine : A member of the class of tryptamines that is the methyl ether derivative of serotonin.

5-Methoxytryptamine: Serotonin derivative proposed as potentiator for hypnotics and sedatives.
aromatic ether;
primary amino compound;
tryptamines
5-hydroxytryptamine 2A receptor agonist;
5-hydroxytryptamine 2B receptor agonist;
5-hydroxytryptamine 2C receptor agonist;
antioxidant;
cardioprotective agent;
human metabolite;
mouse metabolite;
neuroprotective agent;
radiation protective agent;
serotonergic agonist
tacrinetacrine : A member of the class of acridines that is 1,2,3,4-tetrahydroacridine substituted by an amino group at position 9. It is used in the treatment of Alzheimer's disease.

Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders.
acridines;
aromatic amine
EC 3.1.1.7 (acetylcholinesterase) inhibitor
alpha-methylserotoninalpha-methylserotonin: potent agonist at M & D receptors of serotonin; RN given refers to parent cpdtryptaminesserotonergic agonist
ketanserinketanserin : A member of the class of quinazolines that is quinazoline-2,4(1H,3H)-dione which is substituted at position 3 by a 2-[4-(p-fluorobenzoyl)piperidin-1-yl]ethyl group.

Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.
aromatic ketone;
organofluorine compound;
piperidines;
quinazolines
alpha-adrenergic antagonist;
antihypertensive agent;
cardiovascular drug;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
serotonergic antagonist
naratriptannaratriptan: structure given in first sourceheteroarylpiperidine;
sulfonamide;
tryptamines
serotonergic agonist;
vasoconstrictor agent
nimodipinenimodipine : A dihydropyridine that is 1,4-dihydropyridine which is substituted by methyl groups at positions 2 and 6, a (2-methoxyethoxy)carbonyl group at position 3, a m-nitrophenyl group at position 4, and an isopropoxycarbonyl group at position 5. An L-type calcium channel blocker, it acts particularly on cerebral circulation, and is used both orally and intravenously for the prevention and treatment of subarachnoid hemorrhage from ruptured intracranial aneurysm.

Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.
2-methoxyethyl ester;
C-nitro compound;
dicarboxylic acids and O-substituted derivatives;
diester;
dihydropyridine;
isopropyl ester
antihypertensive agent;
calcium channel blocker;
cardiovascular drug;
vasodilator agent
oxymetazolineoxymetazoline : A member of the class of phenols that is 2,4-dimethylphenol which is substituted at positions 3 and 6 by 4,5-dihydro-1H-imidazol-2-ylmethyl and tert-butyl groups, respectively. A direct-acting sympathomimetic with marked alpha-adrenergic activity, it is a vasoconstrictor that is used (generally as the hydrochloride salt) to relieve nasal congestion.

Oxymetazoline: A direct acting sympathomimetic used as a vasoconstrictor to relieve nasal congestion. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1251)
carboxamidine;
imidazolines;
phenols
alpha-adrenergic agonist;
nasal decongestant;
sympathomimetic agent;
vasoconstrictor agent
4-iodoclonidine4-iodoclonidine: structure given in first source
pindololpindolol : A member of the class of indols which is the 2-hydroxy-3-(isopropylamino)propyl ether derivative of 1H-indol-4-ol.

Pindolol: A moderately lipophilic beta blocker (ADRENERGIC BETA-ANTAGONISTS). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638)
indoles;
secondary amine
antiglaucoma drug;
antihypertensive agent;
beta-adrenergic antagonist;
serotonergic antagonist;
vasodilator agent
prazosinprazosin : A member of the class of piperazines that is piperazine substituted by a furan-2-ylcarbonyl group and a 4-amino-6,7-dimethoxyquinazolin-2-yl group at positions 1 and 4 respectively.

Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.
aromatic ether;
furans;
monocarboxylic acid amide;
piperazines;
quinazolines
alpha-adrenergic antagonist;
antihypertensive agent;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor
propranololpropranolol : A propanolamine that is propan-2-ol substituted by a propan-2-ylamino group at position 1 and a naphthalen-1-yloxy group at position 3.

Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.
naphthalenes;
propanolamine;
secondary amine
anti-arrhythmia drug;
antihypertensive agent;
anxiolytic drug;
beta-adrenergic antagonist;
environmental contaminant;
human blood serum metabolite;
vasodilator agent;
xenobiotic
rizatriptanrizatriptan: structure given in first source; RN given refers to benzoatetryptaminesanti-inflammatory drug;
serotonergic agonist;
vasoconstrictor agent
sumatriptansumatriptan : A sulfonamide that consists of N,N-dimethyltryptamine bearing an additional (N-methylsulfamoyl)methyl substituent at position 5. Selective agonist for a vascular 5-HT1 receptor subtype (probably a member of the 5-HT1D family). Used (in the form of its succinate salt) for the acute treatment of migraine with or without aura in adults.

Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of MIGRAINE DISORDERS.
sulfonamide;
tryptamines
serotonergic agonist;
vasoconstrictor agent
tolazolinetolazoline : A member of the class of imidazoles that is 4,5-dihydro-1H-imidazole substituted by a benzyl group.

Tolazoline: A vasodilator that apparently has direct actions on blood vessels and also increases cardiac output. Tolazoline can interact to some degree with histamine, adrenergic, and cholinergic receptors, but the mechanisms of its therapeutic effects are not clear. It is used in treatment of persistent pulmonary hypertension of the newborn.
imidazolesalpha-adrenergic antagonist;
antihypertensive agent;
vasodilator agent
n-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-n-(2-pyridinyl)cyclohexanecarboxamidepiperazines
xylometazolinexylometazoline: RN given refers to parent cpd; structurealkylbenzene
ergotamineergotamine : A peptide ergot alkaloid that is dihydroergotamine in which a double bond replaces the single bond between positions 9 and 10.

Ergotamine: A vasoconstrictor found in ergot of Central Europe. It is a serotonin agonist that has been used as an oxytocic agent and in the treatment of MIGRAINE DISORDERS.
peptide ergot alkaloidalpha-adrenergic agonist;
mycotoxin;
non-narcotic analgesic;
oxytocic;
serotonergic agonist;
vasoconstrictor agent
indopanalpha-methyltryptamine : A tryptamine derivative having a methyl substituent at the alpha-position.

indopan: RN given refers to parent cpd without isomeric designation
tryptamines
metergolinemetergoline : An ergoline alkaloid that is the N-benzyloxycarbonyl derivative of lysergamine. A 5-HT2 antagonist. Also 5-HT1 antagonist and 5-HT1D ligand. Has moderate affinity for 5-HT6 and high affinity for 5-HT7.

Metergoline: A dopamine agonist and serotonin antagonist. It has been used similarly to BROMOCRIPTINE as a dopamine agonist and also for MIGRAINE DISORDERS therapy.
carbamate ester;
ergoline alkaloid
dopamine agonist;
geroprotector;
serotonergic antagonist
sertindolesertindole : A phenylindole that is 1H-indole which is substituted on the nitrogen by a p-chlorophenyl group, at position 5 by chlorine, and at position 3 by a piperidin-4-yl group, which is itself substituted on the nitrogen by a 2-(2-oxoimidazolidin-1-yl)ethyl group.heteroarylpiperidine;
imidazolidinone;
organochlorine compound;
organofluorine compound;
phenylindole
alpha-adrenergic antagonist;
H1-receptor antagonist;
second generation antipsychotic;
serotonergic antagonist
zolmitriptanzolmitriptan : A member of the class of tryptamines that is N,N-dimethyltryptamine in which the hydrogen at position 5 of the indole ring has been replaced by a [(4S)-2-oxo-1,3-oxazolidin-4-yl]methyl group. A serotonin 5-HT1 B and D receptor agonist, it is used for the treatment of migraine.

zolmitriptan: an antimigraine compound; a serotonin (5HT)-1D receptor agonist
oxazolidinone;
tryptamines
anti-inflammatory drug;
serotonergic agonist;
vasoconstrictor agent
frovatriptancarbazoles
eletriptaneletriptan : An N-alkylpyrrolidine, that is N-methylpyrrolidine in which the pro-R hydrogen at position 2 is replaced by a {5-[2-(phenylsulfonyl)ethyl]-1H-indol-3-yl}methyl group.

eletriptan: 5-HT(1B/1D) receptor agonist; structure in first source
indoles;
N-alkylpyrrolidine;
sulfone
non-steroidal anti-inflammatory drug;
serotonergic agonist;
vasoconstrictor agent
xylonidinexylonidine: alpha adrenoreceptor stimulation by above cpd mainly inhibits the release of mediator and/or the bronchoconstriction caused by moderate activation of sensory nerves; forced molting agent; structure given in first source
gr 127935GR 127935 : A member of the class of benzamides obtained by formal condensation of the carboxy group of 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxylic acid and the anilino group of 4-methoxy-3-(4-methylpiperazin-1-yl)aniline. Potent and selective 5-HT1B/1D receptor antagonist (pKi values are 8.5 for both guinea pig 5-HT1D and rat 5-HT1B receptors). Displays > 100-fold selectivity over 5HT1A, 5-HT2A, 5-HT2C receptors and other receptor types. Centrally active following oral administration.

GR 127935: a 5-HT 1D receptor antagonist
1,2,4-oxadiazole;
benzamides;
N-alkylpiperazine;
N-arylpiperazine
pramipexolepramipexole : A member of the class of benzothiazoles that is 4,5,6,7-tetrahydro-1,3-benzothiazole in which the hydrogens at the 2 and 6-pro-S-positions are substituted by amino and propylamino groups, respectively.

Pramipexole: A benzothiazole derivative and dopamine agonist with antioxidant properties that is used in the treatment of PARKINSON DISEASE and RESTLESS LEGS SYNDROME.
benzothiazoles;
diamine
antidyskinesia agent;
antiparkinson drug;
dopamine agonist;
radical scavenger
gr 55562benzamides
cp 122288CP 122288: activates the trigeminovascular receptor blocking neurogenic inflammation within dura mater; a 5-HT1 receptor agonist
harmalanharmalan: structure given in first sourceharmala alkaloid
8-(di-n-propylamino)-6,7,8,9-tetrahydro-3h-benz(e)indole-1-carbaldehyde8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz(e)indole-1-carbaldehyde: RN refers to (+-)-isomer; structure given in first source
nantenine, (+-)-isomer
rs 1274452-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine: a 5-HT(2B) receptor antagonist; structure in first source
1-methyl-6-methoxy-dihydro-beta-carboline
sb-224289SB 224289 : A member of the class of benzamides obtained by formal condensation of the carboxy group of 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxylic acid with the secondary amino group of 1'-methyl-6,7-dihydro-5H-spiro[furo[2,3-f]indole-3,4'-piperidine]. Selective 5-HT1B receptor antagonist (pKi = 8.2). Displays >60-fold selectivity over 5-HT1D, 5-HT1A, 5-HT1E, 5-HT1F, 5-HT2A and 5-HT2C receptors in radioligand binding and functional assays. Centrally active following oral administration in vivo.1,2,4-oxadiazole;
azaspiro compound;
benzamides;
organic heterotetracyclic compound
serotonergic antagonist
harmineharmine : A harmala alkaloid in which the harman skeleton is methoxy-substituted at C-7.

Harmine: Alkaloid isolated from seeds of PEGANUM HARMALA; ZYGOPHYLLACEAE. It is identical to banisterine, or telepathine, from Banisteria caapi and is one of the active ingredients of hallucinogenic drinks made in the western Amazon region from related plants. It has no therapeutic use, but (as banisterine) was hailed as a cure for postencephalitic PARKINSON DISEASE in the 1920's.
harmala alkaloidanti-HIV agent;
EC 1.4.3.4 (monoamine oxidase) inhibitor;
metabolite
ly 344864LY 344864: has selective affinity for the 5-HT1F receptor; structure in first sourcecarbazoles
l 7458703-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine: selective for D(4) receptors; structure in first sourcepiperazines
ly 3343704-fluoro-N-(3-(1-methyl-4-piperidinyl)-1H-indol-5-yl)benzamide: 5-HT(1F) receptor agonist
sb 258719
sb 271046SB 271046: 5-HT(6) receptor antagonist; structure in first source
gr 46611GR 46611: known to lower body temperature in guinea pigs
1-(3-(5-(1,2,4-triazol-4-yl)-1h-indol-3-yl)propyl)-4-(2-(3-fluorophenyl)ethyl)piperazine1-(3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl)-4-(2-(3-fluorophenyl)ethyl)piperazine: an h5-HT(1D) receptor agonist; structure in first source
sb 269970SB 269970: a 5-HT(7) antagonist; structure in first sourcesulfonamide
vilazodonevilazodone : A 1-benzofuran that is 5-(piperazin-1-yl}-1-benzofuran-2-carboxamide having a (5-cyanoindol-3-yl)butyl group attached at position N-4 on the piperazine ring. Used for the treatment of major depressive disorder.1-benzofurans;
indoles;
monocarboxylic acid amide;
N-alkylpiperazine;
N-arylpiperazine;
nitrile
antidepressant;
serotonergic agonist;
serotonin uptake inhibitor
ms-245N,N-dimethyl-2-(1-(benzenesulfonyl)-5-methoxy-1H-indol-3-yl)ethylamine: a 5-HT(6) receptor ligand; structure in first source
n-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamideN-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide: structure in first source
ith 4012
l 772405L 772405: an h5-HT(1D) receptor agonist; structure in first source
sb258741
5-chloro-2,3-dihydro-6-(4-methylpiperazin-1-yl)-1-(4-(pyridin-4-yl)naphth-1-ylaminocarbonyl)-1h-indole
pnu 109291PNU 109291: 5-HT(1D) receptor agonist; structure in first source
4-n-butyl-1-(4-(2-methylphenyl)-4-oxo-1-butyl)-piperidine hydrogen chloride
sb-656104-aSB-656104-A: structure in first source
5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1h-indole5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole: a 5-HT6 agonist; structure in first sourceindoles
sb-649915SB-649915: potent 5-HT1A and 5-HT1B autoreceptor antagonist and 5-HT re-uptake inhibitor
methylhistaprodifen
histaprodifen
sb 328437SB 328437: a CC chemokine receptor-3 antagonist that inhibits binding of eotaxin and monocyte chemotactic protein-4 to eosinophils; structure in first source
naphyrone1-naphthalen-2-yl-2-pyrrolidin-1-ylpentan-1-one: a monoamine uptake inhibitor; structure in first source
col-144lasmiditan: a high-affinity, highly selective serotonin 5-HT(1F) receptor agonist; structure in first source
a 803467A 803467: an Nav1.8 sodium channel blocker; structure in first source
sp 2033-fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile: a radioligand for mGlu5 receptor; structure in first source
n,n-diallyl-5-methoxytryptamineN,N-diallyl-5-methoxytryptamine: structure in first sourcetryptamines