Top ▲

Cav2.2

Click here for help

Target id: 533

Nomenclature: Cav2.2

Family: Voltage-gated calcium channels (CaV)

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 24 0 2339 9q34.3 CACNA1B calcium voltage-gated channel subunit alpha1 B
Mouse 24 0 2327 2 16.58 cM Cacna1b calcium channel, voltage-dependent, N type, alpha 1B subunit
Rat 24 0 2336 3p13 Cacna1b calcium voltage-gated channel subunit alpha1 B
Previous and Unofficial Names Click here for help
CACNL1A5 | CACNN | brain calcium channel III | Cchn1a | α1B | calcium channel
Database Links Click here for help
Alphafold
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
&beta1-4 32,42,52,70
α 70
Other Associated Proteins
Name References
G protein β/γ subunits 20,22,73
Associated Protein Comments
Cav2.2 channels are associated with and regulated by G protein β/γ subunits (reviewed in [9]).
Functional Characteristics Click here for help
N-type calcium current: High voltage-activated, moderate voltage-dependent inactivation
Ion Selectivity and Conductance Click here for help
Species:  Human
Rank order:  Ba2+ [19.0 pS] > Sr2+ > Ca2+
References:  5,8,40
Species:  Rat
Rank order:  Ba2+ [18.0 - 20.0 pS] > Ca2+
References:  11,15,48
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -2.6 0.93 30 Neurons (hippocampus) Rat
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -18.6 – -5.3 - 31,45 Xenopus laevis oocyte Rat
Inactivation  -72.7 – -37.0 100.0 – 800.0 31,45
Comments  Inactivation: τfast = 100-150ms, τslow = 700-800ms
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  9.0 – 18.1 - 12,69 HEK 293 cells. Human
Inactivation  -59.4 – -53.0 46.0 – 453.0 5,12,69
Comments  Inactivation: τfast = 46-105ms, τslow = 291-453ms.
Voltage Dependence Comments
Activation kinetics and current-voltage relations are affected by Cav2.2 alternative splicing [31,45,58]. Activation and inactivation time courses depend upon the nature of the coexpressed β subunit (slower with β2) [45]. Notable Cav2.2 splice variants that affect channel biophysical properties, modulation and interaction with synaptic proteins are found in refs [17,25,31,45,58].

Download all structure-activity data for this target as a CSV file go icon to follow link

Gating inhibitors Click here for help
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
ω-grammotoxin SIA Peptide Click here for species-specific activity table Rn Antagonist - - 5x10-7 -80.0 37
Conc range: 5x10-7 M [37]
Holding voltage: -80.0 mV
kurtoxin Peptide Click here for species-specific activity table Rn Antagonist 6.3 pEC50 - -80.0 53
pEC50 6.3 [53]
Holding voltage: -80.0 mV
NP118809 Small molecule or natural product Rn - 7.0 pIC50 - -80.0 72
pIC50 7.0 (IC50 1.1x10-7 M) [72]
Holding voltage: -80.0 mV
TROX-1 Small molecule or natural product Hs - 5.4 – 6.4 pIC50 - -110.0 – -70.0 1,60
pIC50 5.4 – 6.4 [1,60]
Holding voltage: -110.0 – -70.0 mV
View species-specific gating inhibitor tables
Gating Inhibitor Comments
ω-grammotoxin SIA causes at +100mV shift in the voltage dependence of Cav2.2 containing channels [37].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
ω-conotoxin GVIA Peptide Click here for species-specific activity table Rn Antagonist 10.4 pIC50 - -80.0 29
pIC50 10.4 (IC50 3.8x10-11 M) [29]
Holding voltage: -80.0 mV
ω-conotoxin CVID Peptide Click here for species-specific activity table Rn Antagonist 10.2 pIC50 - - 29
pIC50 10.2 [29]
ω-conotoxin CVIA Peptide Click here for species-specific activity table Rn Antagonist 9.3 pIC50 - - 29
pIC50 9.3 [29]
ziconotide Peptide Approved drug Click here for species-specific activity table Rn Antagonist 7.7 – 10.3 pIC50 - Physiological 3,29
pIC50 7.7 – 10.3 [3,29]
Holding voltage: Physiological
DW13.3 Peptide Click here for species-specific activity table Rn Antagonist 7.7 – 8.6 pIC50 - -100.0 59
pIC50 7.7 – 8.6 [59]
Holding voltage: -100.0 mV
ω-conotoxin CVIB Peptide Click here for species-specific activity table Rn Antagonist 8.1 pIC50 - - 29
pIC50 8.1 [29]
ω-conotoxin CVIC Peptide Click here for species-specific activity table Rn Antagonist 8.1 pIC50 - - 29
pIC50 8.1 [29]
ω-conotoxin MVIIC Peptide Click here for species-specific activity table Rn Antagonist 6.1 – 8.5 pIC50 - -80.0 21,29,38
pIC50 6.1 – 8.5 (IC50 7.94x10-7 – 3.16x10-9 M) [21,29,38]
Holding voltage: -80.0 mV
cilnidipine Small molecule or natural product Approved drug Rn Pore blocker 6.7 pIC50 - -60.0 16
pIC50 6.7 [16]
Holding voltage: -60.0 mV
Pb2+ Click here for species-specific activity table Hs Antagonist 5.9 pIC50 - -90.0 46
pIC50 5.9 [46]
Holding voltage: -90.0 mV
ziconotide Peptide Approved drug Hs Antagonist 1.0 pIC50 - -90.0 25
pIC50 1.0 [25]
Holding voltage: -90.0 mV
View species-specific channel blocker tables
Channel Blocker Comments
The efficacy of ω-conotoxin MVIIC is highly dependent on [Ba2+]. ω-conotoxin GVIA is routinely used at concentrations of 500nM to 1μM to completely and irreversibly block native and cloned N-type currents. Cilnidipine is a dihydropyridine derivative that blocks both N-type and L-type calcium channels and has been used clinically to treat patients with renal and cardiovascular disease [61,71].
Tissue Distribution Click here for help
Brain (hippocampus and parahippocampal gyrus)
Species:  Human
Technique:  Immunocytochemistry
References:  13
Brain (widespread)
Species:  Human
Technique:  Microarray analysis
References:  19
Brain (widespread)
Species:  Mouse
Technique:  In situ hybridisation
References:  28
Brain (cerebral cortex: neurons, oligodendrocyte precursor cells, newly formed oligodendrocytes, myelinating oligodendrocytes)
Species:  Mouse
Technique:  RNA transcriptome
References:  74
Auditory system (spiral ganglion)
Species:  Mouse
Technique:  qPCR, immunocytochemistry
References:  10
Brain (widespread)
Species:  Rat
Technique:  Northern Blot
References:  14,56
Sperm
Species:  Rat
Technique:  Immunocytochemistry, whole cell patch clamp
References:  66
Brain (widespread in the neuronal cell bodies, dendrites and nerve terminals)
Species:  Rat
Technique:  Immunohistochemistry
References:  67
Spinal cord (neuronal cell bodies, dendrites and nerve terminals)
Species:  Rat
Technique:  Immunocytochemistry
References:  68
Cortical astrocytes
Species:  Rat
Technique:  RT-PCR
References:  11
Pituitary (somatotrophs, lactotrophs)
Species:  Rat
Technique:  RT-PCR, immunocytochemistry, whole cell patch clamp
References:  64
Functional Assays Click here for help
Patch clamp (whole cells currents and single channels recordings)
Species:  Rat
Tissue:  PC12 cells
Response measured:  N-type currents
References:  48
Patch clamp (whole cell currents and single channel recordings)
Species:  Rat
Tissue:  Dissociated primary neurons (SCG)
Response measured:  N-type currents
References:  48
Patch clamp (whole cell currents and single channel recordings)
Species:  Rat
Tissue:  Cortical astrocytes
Response measured:  N-type currents
References:  11
Patch clamp (whole cell currents)
Species:  Human
Tissue:  HEK293 cells expressing Cav2.2
Response measured:  N-type currents
References:  5
Two-microelectrode voltage clamp
Species:  Rat
Tissue:  Xenopus laevis oocytes expressing Cav2.2
Response measured:  N-type currents
References:  31,45
Patch clamp (whole cell currents and single channel recordings)
Species:  Rat
Tissue:  Brain slice cultures (hippocampus and cerebellum)
Response measured:  N-type currents
References:  30,49
Measurement of evoked neurotransmitter release.
Species:  Rat
Tissue:  Central synaptosomes (hippocampus and striatum)
Response measured:  KCl-evoked relase of radiloabelled neurostansmitters (noradrenaline and glutamate respectively)
References:  33,63
Measurement of evoked neurotransmitter release
Species:  Rat
Tissue:  Sympathetic neurons
Response measured:  KCl-evoked release of noradrenaline.
References: 
Monitoring of intracellular calcium levels with fluorescent indicators
Species:  Rat
Tissue:  Brain slice cultures
Response measured:  Changes in intracellular calcium levels due to N-type channels
References:  41
Physiological Functions Click here for help
Synaptic transmission
Species:  Rat
Tissue:  Brain (hippocampus, cerebellum, spinal cord
References:  62
Neuronal migration during development
Species:  Mouse
Tissue:  Brain (cerebellum)
References:  27
Ethanol reinforcing and rewarding behaviours
Species:  Mouse
Tissue:  Brain
References:  44
Sympathetic control of the cardiac system
Species:  Mouse
Tissue:  Sympathetic neurons
References:  43
Sympathetic functions (blood pressure control, baroreflex response, temperature regulation
Species:  Mouse
Tissue:  Peripheral neurons
References:  23
Inflammatory and neuropathic pain
Species:  Mouse
Tissue:  Brain and spinal cord
References:  26,51
Long term potentiation and long-term memory
Species:  Mouse
Tissue:  Brain (hippocampus)
References:  24
Inflammatory and neuropathic pain. Note: Cell-specific splicing of mutually exclusive exons (e37a and e37b) of the rat Cacna1b gene affects pain signalling in nociceptive neurons.
Species:  Rat
Tissue:  Brain and spinal cord
References:  2,6,35,54-55,65
Itching/scratching reflex
Species:  Mouse
Tissue:  Spinal chord
References:  34
Physiological Consequences of Altering Gene Expression Click here for help
Absence of Cav2.2 expression leads to abnormal sympathetic control of the cardiovascular system, impaired LTP and long-term memory and responses to ethanol intoxication and nociception; changes to sleep, wakefulness and vigilance
Species:  Mouse
Tissue:  Central and peripheral nervous system
Technique:  Knockout
References:  4,23-24,26,42,44,51
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0004184 abnormal baroreceptor physiology PMID: 11296258 
Cacna1btm1Ttan Cacna1btm1Ttan/Cacna1btm1Ttan
involves: 129S4/SvJae * C57BL/6
MGI:88296  MP:0009745 abnormal behavioral response to xenobiotic PMID: 12962913 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0003484 abnormal channel response PMID: 11496122 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0003484 abnormal channel response PMID: 11520183 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0002805 abnormal conditioned taste aversion behavior PMID: 15525770 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0002802 abnormal discrimination learning PMID: 16939638 
Cacna1btm1Ttan Cacna1btm1Ttan/Cacna1btm1Ttan
involves: 129S4/SvJae * C57BL/6
MGI:88296  MP:0002912 abnormal excitatory postsynaptic potential PMID: 12962913 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0002912 abnormal excitatory postsynaptic potential PMID: 16939638 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0003194 abnormal frequency of paradoxical sleep PMID: 12890773 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0001752 abnormal hypothalamus secretion PMID: 19004821 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0002945 abnormal inhibitory postsynaptic currents PMID: 19004821 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0002063 abnormal learning/memory/conditioning PMID: 16939638 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0001547 abnormal lipid level PMID: 15870896 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0008432 abnormal long term spatial reference memory PMID: 16939638 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0004753 abnormal miniature excitatory postsynaptic currents PMID: 16939638 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0009435 abnormal miniature inhibitory postsynaptic currents PMID: 19004821 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0002272 abnormal nervous system electrophysiology PMID: 19004821 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0002067 abnormal sensory capabilities/reflexes/nociception PMID: 11520183 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0003463 abnormal single cell response PMID: 19004821 
Cacna1btm1.1Dili Cacna1btm1.1Dili/Cacna1btm1.1Dili
involves: 129P2/OlaHsd * C57BL/6 * FVB/N
MGI:88296  MP:0003463 abnormal single cell response PMID: 20852623 
Cacna1btm2.1Dili Cacna1btm2.1Dili/Cacna1btm2.1Dili
involves: 129P2/OlaHsd * C57BL/6 * FVB/N
MGI:88296  MP:0003463 abnormal single cell response PMID: 20852623 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0001501 abnormal sleep pattern PMID: 12890773 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0001463 abnormal spatial learning PMID: 16939638 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0003470 abnormal summary potential PMID: 19004821 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0004183 abnormal sympathetic nervous system physiology PMID: 11296258 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0003635 abnormal synaptic transmission PMID: 19004821 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0002570 alcohol aversion PMID: 15525770 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0003546 decreased alcohol consumption PMID: 15525770 
Cacna1btm1Ttan Cacna1btm1Ttan/Cacna1btm1Ttan
involves: 129S4/SvJae * C57BL/6
MGI:88296  MP:0001364 decreased anxiety-related response PMID: 11350923 
Cacna1btm2.1Dili Cacna1btm2.1Dili/Cacna1btm2.1Dili
involves: 129P2/OlaHsd * C57BL/6 * FVB/N
MGI:88296  MP:0001982 decreased chemically-elicited antinociception PMID: 20852623 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0002696 decreased circulating glucagon level PMID: 15870896 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0002727 decreased circulating insulin level PMID: 15870896 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0005668 decreased circulating leptin level PMID: 15870896 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0002644 decreased circulating triglyceride level PMID: 15870896 
Cacna1btm1Ttan Cacna1btm1Ttan/Cacna1btm1Ttan
involves: 129S4/SvJae * C57BL/6
MGI:88296  MP:0001489 decreased startle reflex PMID: 11350923 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0009751 enhanced behavioral response to alcohol PMID: 15525770 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0009436 fragmentation of sleep/wake states PMID: 12890773 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0001399 hyperactivity PMID: 12890773 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0000231 hypertension PMID: 11296258 
Cacna1btm1Ttan Cacna1btm1Ttan/Cacna1btm1Ttan
involves: 129S4/SvJae * C57BL/6
MGI:88296  MP:0005498 hyporesponsive to tactile stimuli PMID: 11350923 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0005498 hyporesponsive to tactile stimuli PMID: 11520183 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0009755 impaired behavioral response to alcohol PMID: 15525770 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0009712 impaired conditioned place preference behavior PMID: 15525770 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0002969 impaired social transmission of food preference PMID: 16939638 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0005292 improved glucose tolerance PMID: 15870896 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0001353 increased aggression towards mice PMID: 19004821 
Cacna1btm1Ttan Cacna1btm1Ttan/Cacna1btm1Ttan
involves: 129S4/SvJae * C57BL/6
MGI:88296  MP:0008531 increased chemical nociceptive threshold PMID: 11350923 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0008531 increased chemical nociceptive threshold PMID: 11496122 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0008531 increased chemical nociceptive threshold PMID: 11520183 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0002626 increased heart rate PMID: 11296258 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0005659 increased resistance to diet-induced obesity PMID: 15870896 
Cacna1btm1Ksw Cacna1btm1Ksw/Cacna1btm1Ksw
involves: C57BL/6 * CBA
MGI:88296  MP:0001973 increased thermal nociceptive threshold PMID: 11496122 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0001973 increased thermal nociceptive threshold PMID: 11520183 
Cacna1btm1Ttan Cacna1btm1Ttan/Cacna1btm1Ttan
involves: 129S4/SvJae * C57BL/6
MGI:88296  MP:0002082 postnatal lethality PMID: 11350923 
Cacna1btm1.1Dili Cacna1btm1.1Dili/Cacna1btm1.1Dili
involves: 129P2/OlaHsd * C57BL/6 * FVB/N
MGI:88296  MP:0002082 postnatal lethality PMID: 20852623 
Cacna1btm1Hssh Cacna1btm1Hssh/Cacna1btm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88296  MP:0001473 reduced long term potentiation PMID: 16939638 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Chronic neuropathic pain
Drugs: 
Side effects:  Cognitive impairment, hallucinations, changes in mood and consciousness
Therapeutic use:  Opioid-unresponsive chronic pain
References:  7,36,39,47,57
Disease:  Kleefstra syndrome
OMIM: 610253
Disease:  Neurodevelopmental Disorder With Seizures And Nonepileptic Hyperkinetic Movements; NEDNEH
OMIM: 618497
Role: 
References:  18
Disease:  Spinal cord injury
Drugs: 
Therapeutic use:  Treatment of severe spasticity after spinal cord injury
References:  50

References

Show »

1. Abbadie C, McManus OB, Sun SY, Bugianesi RM, Dai G, Haedo RJ, Herrington JB, Kaczorowski GJ, Smith MM, Swensen AM et al.. (2010) Analgesic effects of a substituted N-triazole oxindole (TROX-1), a state-dependent, voltage-gated calcium channel 2 blocker. J Pharmacol Exp Ther, 334 (2): 545-55. [PMID:20439438]

2. Bell TJ, Thaler C, Castiglioni AJ, Helton TD, Lipscombe D. (2004) Cell-specific alternative splicing increases calcium channel current density in the pain pathway. Neuron, 41 (1): 127-38. [PMID:14715140]

3. Benjamin ER, Pruthi F, Olanrewaju S, Shan S, Hanway D, Liu X, Cerne R, Lavery D, Valenzano KJ, Woodward RM et al.. (2006) Pharmacological characterization of recombinant N-type calcium channel (Cav2.2) mediated calcium mobilization using FLIPR. Biochem Pharmacol, 72 (6): 770-82. [PMID:16844100]

4. Beuckmann CT, Sinton CM, Miyamoto N, Ino M, Yanagisawa M. (2003) N-type calcium channel alpha1B subunit (Cav2.2) knock-out mice display hyperactivity and vigilance state differences. J Neurosci, 23 (17): 6793-7. [PMID:12890773]

5. Bleakman D, Bowman D, Bath CP, Brust PF, Johnson EC, Deal CR, Miller RJ, Ellis SB, Harpold MM, Hans M et al.. (1995) Characteristics of a human N-type calcium channel expressed in HEK293 cells. Neuropharmacology, 34 (7): 753-65. [PMID:8532142]

6. Bowersox SS, Gadbois T, Singh T, Pettus M, Wang YX, Luther RR. (1996) Selective N-type neuronal voltage-sensitive calcium channel blocker, SNX-111, produces spinal antinociception in rat models of acute, persistent and neuropathic pain. J Pharmacol Exp Ther, 279 (3): 1243-9. [PMID:8968347]

7. Brose WG, Gutlove DP, Luther RR, Bowersox SS, McGuire D. (1997) Use of intrathecal SNX-111, a novel, N-type, voltage-sensitive, calcium channel blocker, in the management of intractable brachial plexus avulsion pain. Clin J Pain, 13 (3): 256-9. [PMID:9303259]

8. Carabelli V, Lovallo M, Magnelli V, Zucker H, Carbone E. (1996) Voltage-dependent modulation of single N-Type Ca2+ channel kinetics by receptor agonists in IMR32 cells. Biophys J, 70 (5): 2144-54. [PMID:9172738]

9. Catterall WA, Few AP. (2008) Calcium channel regulation and presynaptic plasticity. Neuron, 59 (6): 882-901. [PMID:18817729]

10. Chen WC, Xue HZ, Hsu YL, Liu Q, Patel S, Davis RL. (2011) Complex distribution patterns of voltage-gated calcium channel α-subunits in the spiral ganglion. Hear Res, 278 (1-2): 52-68. [PMID:21281707]

11. D'Ascenzo M, Vairano M, Andreassi C, Navarra P, Azzena GB, Grassi C. (2004) Electrophysiological and molecular evidence of L-(Cav1), N- (Cav2.2), and R- (Cav2.3) type Ca2+ channels in rat cortical astrocytes. Glia, 45 (4): 354-63. [PMID:14966867]

12. Dai G, Haedo RJ, Warren VA, Ratliff KS, Bugianesi RM, Rush A, Williams ME, Herrington J, Smith MM, McManus OB et al.. (2008) A high-throughput assay for evaluating state dependence and subtype selectivity of Cav2 calcium channel inhibitors. Assay Drug Dev Technol, 6 (2): 195-212. [PMID:18471074]

13. Day NC, Shaw PJ, McCormack AL, Craig PJ, Smith W, Beattie R, Williams TL, Ellis SB, Ince PG, Harpold MM et al.. (1996) Distribution of alpha 1A, alpha 1B and alpha 1E voltage-dependent calcium channel subunits in the human hippocampus and parahippocampal gyrus. Neuroscience, 71 (4): 1013-24. [PMID:8684604]

14. Dubel SJ, Starr TV, Hell J, Ahlijanian MK, Enyeart JJ, Catterall WA, Snutch TP. (1992) Molecular cloning of the alpha-1 subunit of an omega-conotoxin-sensitive calcium channel. Proc Natl Acad Sci USA, 89 (11): 5058-62. [PMID:1317580]

15. Feng ZP, Hamid J, Doering C, Jarvis SE, Bosey GM, Bourinet E, Snutch TP, Zamponi GW. (2001) Amino acid residues outside of the pore region contribute to N-type calcium channel permeation. J Biol Chem, 276 (8): 5726-30. [PMID:11120735]

16. Fujii S, Kameyama K, Hosono M, Hayashi Y, Kitamura K. (1997) Effect of cilnidipine, a novel dihydropyridine Ca++-channel antagonist, on N-type Ca++ channel in rat dorsal root ganglion neurons. J Pharmacol Exp Ther, 280 (3): 1184-91. [PMID:9067302]

17. Ghasemzadeh MB, Pierce RC, Kalivas PW. (1999) The monoamine neurons of the rat brain preferentially express a splice variant of alpha1B subunit of the N-type calcium channel. J Neurochem, 73 (4): 1718-23. [PMID:10501220]

18. Gorman KM, Meyer E, Grozeva D, Spinelli E, McTague A, Sanchis-Juan A, Carss KJ, Bryant E, Reich A, Schneider AL et al.. (2019) Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia. Am J Hum Genet, 104 (5): 948-956. [PMID:30982612]

19. Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, van de Lagemaat LN, Smith KA, Ebbert A, Riley ZL et al.. (2012) An anatomically comprehensive atlas of the adult human brain transcriptome. Nature, 489 (7416): 391-9. [PMID:22996553]

20. Herlitze S, Garcia DE, Mackie K, Hille B, Scheuer T, Catterall WA. (1996) Modulation of Ca2+ channels by G-protein beta gamma subunits. Nature, 380 (6571): 258-62. [PMID:8637576]

21. Hillyard DR, Monje VD, Mintz IM, Bean BP, Nadasdi L, Ramachandran J, Miljanich G, Azimi-Zoonooz A, McIntosh JM, Cruz LJ. (1992) A new Conus peptide ligand for mammalian presynaptic Ca2+ channels. Neuron, 9 (1): 69-77. [PMID:1352986]

22. Ikeda SR. (1996) Voltage-dependent modulation of N-type calcium channels by G-protein beta gamma subunits. Nature, 380 (6571): 255-8. [PMID:8637575]

23. Ino M, Yoshinaga T, Wakamori M, Miyamoto N, Takahashi E, Sonoda J, Kagaya T, Oki T, Nagasu T, Nishizawa Y et al.. (2001) Functional disorders of the sympathetic nervous system in mice lacking the alpha 1B subunit (Cav 2.2) of N-type calcium channels. Proc Natl Acad Sci USA, 98 (9): 5323-8. [PMID:11296258]

24. Jeon D, Kim C, Yang YM, Rhim H, Yim E, Oh U, Shin HS. (2007) Impaired long-term memory and long-term potentiation in N-type Ca2+ channel-deficient mice. Genes Brain Behav, 6 (4): 375-88. [PMID:16939638]

25. Kaneko S, Cooper CB, Nishioka N, Yamasaki H, Suzuki A, Jarvis SE, Akaike A, Satoh M, Zamponi GW. (2002) Identification and characterization of novel human Ca(v)2.2 (alpha 1B) calcium channel variants lacking the synaptic protein interaction site. J Neurosci, 22 (1): 82-92. [PMID:11756491]

26. Kim C, Jun K, Lee T, Kim SS, McEnery MW, Chin H, Kim HL, Park JM, Kim DK, Jung SJ et al.. (2001) Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel. Mol Cell Neurosci, 18 (2): 235-45. [PMID:11520183]

27. Komuro H, Rakic P. (1992) Selective role of N-type calcium channels in neuronal migration. Science, 257 (5071): 806-9. [PMID:1323145]

28. Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ et al.. (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature, 445 (7124): 168-76. [PMID:17151600]

29. Lewis RJ, Nielsen KJ, Craik DJ, Loughnan ML, Adams DA, Sharpe IA, Luchian T, Adams DJ, Bond T, Thomas L et al.. (2000) Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes. J Biol Chem, 275 (45): 35335-44. [PMID:10938268]

30. Li L, Bischofberger J, Jonas P. (2007) Differential gating and recruitment of P/Q-, N-, and R-type Ca2+ channels in hippocampal mossy fiber boutons. J Neurosci, 27 (49): 13420-9. [PMID:18057200]

31. Lin Z, Lin Y, Schorge S, Pan JQ, Beierlein M, Lipscombe D. (1999) Alternative splicing of a short cassette exon in alpha1B generates functionally distinct N-type calcium channels in central and peripheral neurons. J Neurosci, 19 (13): 5322-31. [PMID:10377343]

32. Liu H, De Waard M, Scott VE, Gurnett CA, Lennon VA, Campbell KP. (1996) Identification of three subunits of the high affinity omega-conotoxin MVIIC-sensitive Ca2+ channel. J Biol Chem, 271 (23): 13804-10. [PMID:8662888]

33. Luebke JI, Dunlap K, Turner TJ. (1993) Multiple calcium channel types control glutamatergic synaptic transmission in the hippocampus. Neuron, 11 (5): 895-902. [PMID:7902110]

34. Maciel IS, Azevedo VM, Pereira TC, Bogo MR, Souza AH, Gomez MV, Campos MM. (2014) The spinal inhibition of N-type voltage-gated calcium channels selectively prevents scratching behavior in mice. Neuroscience, 277: 794-805. [PMID:25108164]

35. Malmberg AB, Yaksh TL. (1994) Voltage-sensitive calcium channels in spinal nociceptive processing: blockade of N- and P-type channels inhibits formalin-induced nociception. J Neurosci, 14 (8): 4882-90. [PMID:8046458]

36. Mathur VS. (2000) A new pharmacological class of drug for the management of pain. Seminars in Anesthesia, Perioperative Medicine and Pain, 19: 67-75.

37. McDonough SI, Lampe RA, Keith RA, Bean BP. (1997) Voltage-dependent inhibition of N- and P-type calcium channels by the peptide toxin omega-grammotoxin-SIA. Mol Pharmacol, 52 (6): 1095-104. [PMID:9415720]

38. McDonough SI, Swartz KJ, Mintz IM, Boland LM, Bean BP. (1996) Inhibition of calcium channels in rat central and peripheral neurons by omega-conotoxin MVIIC. J Neurosci, 16 (8): 2612-23. [PMID:8786437]

39. McGuire D, Bowersox S, Fellmann JD, Luther RR. (1997) Sympatholysis after neuron-specific, N-type, voltage-sensitive calcium channel blockade: first demonstration of N-channel function in humans. J Cardiovasc Pharmacol, 30 (3): 400-3. [PMID:9300326]

40. McNaughton NC, Randall AD. (1997) Electrophysiological properties of the human N-type Ca2+ channel: I. Channel gating in Ca2+, Ba2+ and Sr2+ containing solutions. Neuropharmacology, 36 (7): 895-915. [PMID:9257935]

41. Mintz IM, Sabatini BL, Regehr WG. (1995) Calcium control of transmitter release at a cerebellar synapse. Neuron, 15 (3): 675-88. [PMID:7546746]

42. Murakami M, Nakagawasai O, Yanai K, Nunoki K, Tan-No K, Tadano T, Iijima T. (2007) Modified behavioral characteristics following ablation of the voltage-dependent calcium channel beta3 subunit. Brain Res, 1160: 102-12. [PMID:17588550]

43. Murakami M, Ohba T, Wu TW, Fujisawa S, Suzuki T, Takahashi Y, Takahashi E, Watanabe H, Miyoshi I, Ono K et al.. (2007) Modified sympathetic regulation in N-type calcium channel null-mouse. Biochem Biophys Res Commun, 354 (4): 1016-20. [PMID:17275790]

44. Newton PM, Orr CJ, Wallace MJ, Kim C, Shin HS, Messing RO. (2004) Deletion of N-type calcium channels alters ethanol reward and reduces ethanol consumption in mice. J Neurosci, 24 (44): 9862-9. [PMID:15525770]

45. Pan JQ, Lipscombe D. (2000) Alternative splicing in the cytoplasmic II-III loop of the N-type Ca channel alpha 1B subunit: functional differences are beta subunit-specific. J Neurosci, 20 (13): 4769-75. [PMID:10864934]

46. Peng S, Hajela RK, Atchison WD. (2002) Characteristics of block by Pb2+ of function of human neuronal L-, N-, and R-type Ca2+ channels transiently expressed in human embryonic kidney 293 cells. Mol Pharmacol, 62 (6): 1418-30. [PMID:12435810]

47. Penn RD, Paice JA. (2000) Adverse effects associated with the intrathecal administration of ziconotide. Pain, 85 (1-2): 291-6. [PMID:10692631]

48. Plummer MR, Logothetis DE, Hess P. (1989) Elementary properties and pharmacological sensitivities of calcium channels in mammalian peripheral neurons. Neuron, 2 (5): 1453-63. [PMID:2560643]

49. Regehr WG, Mintz IM. (1994) Participation of multiple calcium channel types in transmission at single climbing fiber to Purkinje cell synapses. Neuron, 12 (3): 605-13. [PMID:8155322]

50. Ridgeway B, Wallace M, Gerayli A. (2000) Ziconotide for the treatment of severe spasticity after spinal cord injury. Pain, 85 (1-2): 287-9. [PMID:10692630]

51. Saegusa H, Kurihara T, Zong S, Kazuno A, Matsuda Y, Nonaka T, Han W, Toriyama H, Tanabe T. (2001) Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel. EMBO J, 20 (10): 2349-56. [PMID:11350923]

52. Scott VE, De Waard M, Liu H, Gurnett CA, Venzke DP, Lennon VA, Campbell KP. (1996) Beta subunit heterogeneity in N-type Ca2+ channels. J Biol Chem, 271 (6): 3207-12. [PMID:8621722]

53. Sidach SS, Mintz IM. (2002) Kurtoxin, a gating modifier of neuronal high- and low-threshold ca channels. J Neurosci, 22 (6): 2023-34. [PMID:11896142]

54. Sluka KA. (1998) Blockade of N- and P/Q-type calcium channels reduces the secondary heat hyperalgesia induced by acute inflammation. J Pharmacol Exp Ther, 287 (1): 232-7. [PMID:9765342]

55. Smith MT, Cabot PJ, Ross FB, Robertson AD, Lewis RJ. (2002) The novel N-type calcium channel blocker, AM336, produces potent dose-dependent antinociception after intrathecal dosing in rats and inhibits substance P release in rat spinal cord slices. Pain, 96 (1-2): 119-27. [PMID:11932068]

56. Snutch TP, Leonard JP, Gilbert MM, Lester HA, Davidson N. (1990) Rat brain expresses a heterogeneous family of calcium channels. Proc Natl Acad Sci USA, 87 (9): 3391-3395. [PMID:1692134]

57. Staats PS, Yearwood T, Charapata SG, Presley RW, Wallace MS, Byas-Smith M, Fisher R, Bryce DA, Mangieri EA, Luther RR et al.. (2004) Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA, 291 (1): 63-70. [PMID:14709577]

58. Stea A, Dubel SJ, Snutch TP. (1999) alpha 1B N-type calcium channel isoforms with distinct biophysical properties. Ann N Y Acad Sci, 868: 118-30. [PMID:10414290]

59. Sutton KG, Siok C, Stea A, Zamponi GW, Heck SD, Volkmann RA, Ahlijanian MK, Snutch TP. (1998) Inhibition of neuronal calcium channels by a novel peptide spider toxin, DW13.3. Mol Pharmacol, 54 (2): 407-18. [PMID:9687583]

60. Swensen AM, Herrington J, Bugianesi RM, Dai G, Haedo RJ, Ratliff KS, Smith MM, Warren VA, Arneric SP, Eduljee C et al.. (2012) Characterization of the substituted N-triazole oxindole TROX-1, a small-molecule, state-dependent inhibitor of Ca(V)2 calcium channels. Mol Pharmacol, 81 (3): 488-97. [PMID:22188924]

61. Takahara A. (2009) Cilnidipine: a new generation Ca channel blocker with inhibitory action on sympathetic neurotransmitter release. Cardiovasc Ther, 27 (2): 124-39. [PMID:19426250]

62. Takahashi T, Momiyama A. (1993) Different types of calcium channels mediate central synaptic transmission. Nature, 366 (6451): 156-8. [PMID:7901765]

63. Turner TJ, Adams ME, Dunlap K. (1993) Multiple Ca2+ channel types coexist to regulate synaptosomal neurotransmitter release. Proc Natl Acad Sci USA, 90 (20): 9518-22. [PMID:8415733]

64. Tzour A, Sosial E, Meir T, Canello T, Naveh-Many T, Gabizon R, Nussinovitch I. (2013) Multiple pathways for high voltage-activated ca(2+) influx in anterior pituitary lactotrophs and somatotrophs. J Neuroendocrinol, 25 (1): 76-86. [PMID:22882461]

65. Wang YX, Pettus M, Gao D, Phillips C, Scott Bowersox S. (2000) Effects of intrathecal administration of ziconotide, a selective neuronal N-type calcium channel blocker, on mechanical allodynia and heat hyperalgesia in a rat model of postoperative pain. Pain, 84 (2-3): 151-8. [PMID:10666519]

66. Wennemuth G, Westenbroek RE, Xu T, Hille B, Babcock DF. (2000) CaV2.2 and CaV2.3 (N- and R-type) Ca2+ channels in depolarization-evoked entry of Ca2+ into mouse sperm. J Biol Chem, 275 (28): 21210-7. [PMID:10791962]

67. Westenbroek RE, Hell JW, Warner C, Dubel SJ, Snutch TP, Catterall WA. (1992) Biochemical properties and subcellular distribution of an N-type calcium channel alpha 1 subunit. Neuron, 9 (6): 1099-115. [PMID:1334419]

68. Westenbroek RE, Hoskins L, Catterall WA. (1998) Localization of Ca2+ channel subtypes on rat spinal motor neurons, interneurons, and nerve terminals. J Neurosci, 18 (16): 6319-30. [PMID:9698323]

69. Williams ME, Brust PF, Feldman DH, Patthi S, Simerson S, Maroufi A, McCue AF, Veliçelebi G, Ellis SB, Harpold MM. (1992) Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel. Science, 257 (5068): 389-95. [PMID:1321501]

70. Witcher DR, De Waard M, Campbell KP. (1993) Characterization of the purified N-type Ca2+ channel and the cation sensitivity of omega-conotoxin GVIA binding. Neuropharmacology, 32 (11): 1127-39. [PMID:8107967]

71. Xu G, Wu H, Du B, Qin L. (2012) The efficacy and safety of cilnidipine on mild to moderate essential hypertension: a systematic review and meta-analysis of randomized controlled trials in Chinese patients. Cardiovasc Hematol Disord Drug Targets, 12 (1): 56-62. [PMID:22746347]

72. Zamponi GW, Feng ZP, Zhang L, Pajouhesh H, Ding Y, Belardetti F, Pajouhesh H, Dolphin D, Mitscher LA, Snutch TP. (2009) Scaffold-based design and synthesis of potent N-type calcium channel blockers. Bioorg Med Chem Lett, 19 (22): 6467-72. [PMID:19815411]

73. Zamponi GW, Snutch TP. (1998) Decay of prepulse facilitation of N type calcium channels during G protein inhibition is consistent with binding of a single Gbeta subunit. Proc Natl Acad Sci U S A, 95 (7): 4035-9. [PMID:9520488]

74. Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O'Keeffe S, Phatnani HP, Guarnieri P, Caneda C, Ruderisch N et al.. (2014) An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex. J Neurosci, 34 (36): 11929-47. [PMID:25186741]

Contributors

Show »

How to cite this page