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Cav1.2

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 529

Nomenclature: Cav1.2

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 4 2221 12p13.33 CACNA1C calcium voltage-gated channel subunit alpha1 C
Mouse 24 4 2139 6 55.86 cM Cacna1c calcium channel, voltage-dependent, L type, alpha 1C subunit
Rat 24 4 2169 4q42 Cacna1c calcium voltage-gated channel subunit alpha1 C
Previous and Unofficial Names Click here for help
α1C | cardiac or smooth muscle dihydropyridine receptor | cardiac or smooth muscle L-type Ca2+ channel | CACH2 | CACN2 | CACNL1A1 | LQT8 | calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle | L-type calcium channel alpha-1 subunit | calcium channel, voltage-dependent, L type, alpha 1C subunit | calcium channel
Database Links Click here for help
Alphafold
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
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
β1-4 21
α (isoforms 1-4) 43,72
Other Associated Proteins
Name References
STIM-1 63,91
A-kinase anchoring proteins 18
BIN-1 37
PP2A/PP2B/Calcineurin 32,59,100
Calmodulin-dependent kinase II 46,69
Caveolin 3 5
KCHIP-2 86
Phospholemman/FXYD1 90
Sorcin 22
Calcium binding proteins (Caldendrin, CaBP1) 87
NIL-16 95
Phosphodiesterase 4B 47
Calmodulin 67,69,104,107
Calfacilitin 62
alpha-actinin 31
RGK-GTPases 50,61,103
Functional Characteristics Click here for help
L-type calcium current: High voltage-activated, voltage- and calcium-dependent inactivation
Ion Selectivity and Conductance Click here for help
Species:  Guinea pig
Rank order:  Na+ [85.0 pS] > Li+ [45.0 pS] > Ba2+ [25.0 pS] > Ca2+ [8.0 pS] = Sr2+ [8.0 pS]
References:  34
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -17.6 0.5 – 1.5 33 HEK-293, tsA-201 Mouse
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  0.9 - 88 Xenopus laevis oocyte Human
Inactivation  -14.9 - 88
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -6.0 – -0.1 (median: -4.8) 5.2 – 7.1 13,48,53,55,65 Ventricular myocytes. Human
Inactivation  -28.5 – -18.4 (median: -20.4) 9.11 – 21.1 9,13,48,53,55,65
Comments  Data are given for physiological Ca2+ concentrations. Inactivation time constants are given for depolarising pulses close to Vmax. In addition to τf displayed above τs is 60.9-133ms. The activation time data is measured time to peak during pulses close to Vmax.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  4.5 - 15 Xenopus laevis oocyte Rat
Inactivation  1.7 30.0 15
Comments  Data are for 10mM extracellular Ca2+ concentrations. Inactivation time constant ii estimated given for depolarising pulses close to Vmax. In addition to τf displayed above τs is 175ms.
Voltage Dependence Comments
V0.5 for inactivation varies depending on prepulse duration (more negative after long prepulses); inactivation time course strongly depends on associated β subunit (slower inactivation with β2a) and on charge carrier (calcium-induced inactivation with Ca2+ as charge carrier). Activation and inactivation voltage are affected by alternative splicing. Splice variants preferentially expressed in vascular smooth muscle activate/inactivate at more hyperpolarized voltages. They underlie hyperpolarized window currents in smooth muscle and enhanced state-dependent inhibition by dihydropyridine calcium channel blockers [49].

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Activators
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
BAYK 8644 Small molecule or natural product Click here for species-specific activity table Rn - - - 5x10-6 - 15
Conc range: 5x10-6 M [15]
FPL64176 Small molecule or natural product Click here for species-specific activity table Hs - - - 1x10-7 - 1x10-6 - 42,51
Conc range: 1x10-7 - 1x10-6 M [42,51]
Description: guinea pig, human stem cell-derived cardiomyocytes
(-)-(S)-BayK8644 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - ~7.8 pEC50 - -
pEC50 ~7.8 (EC50 ~1.73x10-8 M)
SZ(+)-(S)-202-791 Small molecule or natural product Click here for species-specific activity table Hs - - - - -
View species-specific activator tables
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
[3H](+)-isradipine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 10.1 – 11.0 pKd - - 78
pKd 10.1 – 11.0 [78]
[3H](+)-isradipine Small molecule or natural product Ligand is labelled Ligand is radioactive Mm Antagonist 10.1 pKd - - 80
pKd 10.1 [80]
[3H](-)devapamil Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 8.2 – 8.4 pKd - - 58,106
pKd 8.2 – 8.4 [58,106]
[3H](+)-cis-diltiazem Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 7.2 pKd - - 58
pKd 7.2 [58]
nitrendipine Small molecule or natural product Approved drug Clf Antagonist 9.4 pIC50 - -80.0 – 30.0 8
pIC50 9.4 [8]
Holding voltage: -80.0 – 30.0 mV
amlodipine Small molecule or natural product Approved drug Oc - 9.3 pIC50 - - 38
pIC50 9.3 [38]
Description: Determined in vascular smooth muscle.
isradipine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.5 – 8.8 pIC50 - - 60
pIC50 8.8 arterial smooth muscle-like activity [60]
pIC50 8.5 dopamine neuron neuron-like activity [60]
nifedipine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 8.1 – 8.7 pIC50 - -40.0 68,71
pIC50 8.1 – 8.7 (IC50 8.9x10-9 – 2x10-9 M) 100-fold difference for nifedipine on rat smooth (pIC50 8.5) versus cardiac (pIC50 6.5) cells in vitro (Perez-Vizcaino et al. 1993). [68,71]
Holding voltage: -40.0 mV
Description: guinea pig, human stem cell-derived cardiomyocytes
nisoldipine Small molecule or natural product Approved drug Click here for species-specific activity table Mm Antagonist 7.0 – 8.0 pIC50 - -80.0 79
pIC50 7.0 – 8.0 [79]
Holding voltage: -80.0 mV
isradipine Small molecule or natural product Approved drug Click here for species-specific activity table Mm Antagonist 7.5 pIC50 - -80.0 80
pIC50 7.5 [80]
Holding voltage: -80.0 mV
(-)-devapamil Small molecule or natural product Rn Antagonist 7.3 pIC50 - 10.0 36,40
pIC50 7.3 [36,40]
Holding voltage: 10.0 mV
nisoldipine Small molecule or natural product Approved drug Hs Antagonist 7.1 pIC50 - -80.0 83
pIC50 7.1 [83]
Holding voltage: -80.0 mV
nimodipine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 6.8 pIC50 - -80.0 101
pIC50 6.8 [101]
Holding voltage: -80.0 mV
verapamil Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 5.3 – 6.5 pIC50 - -60.0 – 10.0 40
pIC50 5.3 – 6.5 [40]
Holding voltage: -60.0 – 10.0 mV
View species-specific gating inhibitor tables
Gating Inhibitor Comments
Inhibition by dihydropyridines (e.g. nifedipine or isradipine; [49,60,68]) is voltage-dependent with a higher apparent affinity at more depolarised potentials; phenylalkylamines (like devapamil; [40]) exhibit strong use-dependence with a higher apparent affinity at higher stimulation frequencies.
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
calciseptine Peptide Hs Antagonist 7.1 – 7.8 pIC50 - - 7,19,92
pIC50 7.1 – 7.8 [7,19,92]
Pb2+ Click here for species-specific activity table Hs Antagonist 6.4 pIC50 - -70.0 66
pIC50 6.4 [66]
Holding voltage: -70.0 mV
diltiazem Small molecule or natural product Approved drug Ligand has a PDB structure Mf Antagonist 6.3 pIC50 - - 41
pIC50 6.3 [41]
verapamil Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Rn Antagonist 5.3 – 6.5 pIC50 - - 40
pIC50 5.3 – 6.5 [40]
Cd2+ Click here for species-specific activity table Oc - 5.7 – 6.0 pIC50 - -80.0 35
pIC50 5.7 – 6.0 [35]
Holding voltage: -80.0 mV
benidipine Small molecule or natural product Approved drug Hs Antagonist 5.3 pIC50 - - 99
pIC50 5.3 (IC50 4.9x10-6 M) [99]
Description: Inhibition of human L-type calcium channel Cav1.2 in Xenopus oocyte, measured using 2-electrode voltage-clamp.
mibefradil Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.9 pIC50 - -110.0 54
pIC50 4.9 [54]
Holding voltage: -110.0 mV
(-)-(R)-efonidipine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 2.0 – 3.5 pIC50 - -100.0 – -60.0 26
pIC50 2.0 – 3.5 [26]
Holding voltage: -100.0 – -60.0 mV
View species-specific channel blocker tables
Channel Blocker Comments
Amlodopine, isradipine, nifedipine, nitrendipine, and nimodipine are examples of dihydropyridine calcium channel antagonists. Verapamil is a phenylalkylamine calcium channel blocker. Diltiazem is a benzothiazepine calcium channel blocker.
Immunopharmacology Comments
Cav1.2 is implicated in Th2 cell function in asthma [75,89].
Cell Type Associations
Immuno Cell Type:  T cells
Cell Ontology Term:   T-helper 2 cell (CL:0000546)
References:  74-75,89
Immuno Process Associations
Immuno Process:  Immune system development
Tissue Distribution Click here for help
Brain (cortex, pallidum, putamen, hippocampus, caudate nucleas, substantia nigra, cerebellar cortex, dentate nucleus, spinal cord, dorsal root ganglia).
Species:  Human
Technique:  RT-PCR
References:  85
Heart, brain, prostate, bladder,uterus ,stomach, colon, small intestive, placenta, adrenal gland, spinal cord.
Species:  Human
Technique:  Northern Blot
References:  30,77,83
Lymphocytes
Species:  Human
Technique:  RT-PCR, Western blotting.
References:  84
Lymphocytes
Species:  Mouse
Technique:  RT-PCR
References:  4
Expressed in the first and second pharyngeal arches within the subset of cells that give rise to jaw primordia.
Species:  Mouse
Technique:  β-galactosidase expression in transgenic mice
References:  73
Brain (adult; hippocampus, cerebellum, amygdala, thalamus, hypothalamus, caudate putamen, cortex), heart. Teeth (P0), eye (E16.5, retina and sclera), digits (E12.5).
Species:  Mouse
Technique:  In situ hybridisation
References:  83
Brain (cerebellum, olfactory bulb, hippocampus (dentate gyrus and Ammon's horn) > amygdala, thalamus).
Species:  Rat
Technique:  In situ hybridisation
References:  52
Tissue Distribution Comments
The physiological role of individual L-type channel isoforms for lymphocyte function not established. Additionally, truncated Cav1.2 protein has been detected in lymphocytes on protein level, however its function remains unknown [84].
Functional Assays Click here for help
Calcium imaging.
Species:  Rat
Tissue:  Cardiac myocytes.
Response measured:  Intracellular calcium transients, calcium release.
References:  14,29
Patch-clamp (whole cell currents and single channel recordings), two-electrode voltage-clamp.
Species:  Human
Tissue:  Cardiac myocytes.
Response measured:  L-type currents
References:  9,13,30,48,53,55,65,80
Patch-clamp (whole cell currents and single channel recordings), two-electrode voltage-clamp.
Species:  Rat
Tissue:  Xenopus oocytes, HEK293 cells, PC12 cells expressing Cav1.2.
Response measured:  L-type currents.
References:  15,36,40,51
Patch-clamp (whole cell currents and single channel recordings), two-electrode voltage-clamp.
Species:  Human
Tissue:  Xenopus oocytes, CHO cells expressing Cav1.2
Response measured:  L-type current
References:  77,81,83,88
Patch-clamp (whole cell currents and single channel recordings), two-electrode voltage-clamp.
Species:  Rat
Tissue:  Sympathetic neurons.
Response measured:  L-type current
References:  51
Patch-clamp (whole cell currents and single channel recordings), two-electrode voltage-clamp.
Species:  Mouse
Tissue:  HEK-293 cells expressing Cav1.2, cardiac myocytes
Response measured:  L-type currents.
References:  33,60,79
Physiological Functions Click here for help
Excitation contraction coupling and muscle contraction in heart and vascular smooth muscle.
Species:  Mouse
Tissue:  Heart and vascular smooth muscle.
References:  57,80,105
Insulin secretion, β-cell L-type calcium currents.
Species:  Mouse
Tissue:  Pancreatic β-cells.
References:  6,76,80
Early cardiac development.
Species:  Mouse
Tissue:  Embryonal heart.
References:  79
Urinary bladder function.
Species:  Mouse
Tissue:  Urinary bladder.
References:  94
Mandibular development (evidence in humans and mice)
Species:  Human
Tissue:  First and second pharyngeal arches (jaw primordia)
References:  73
Control of emotional behaviours
Species:  Mouse
Tissue:  Brain
References:  3,45
Acquisition of conditioned fear, fear learning
Species:  Mouse
Tissue:  Brain
References:  39,44
Hippocampal long-term potentiation and spatial memory.
Species:  Mouse
Tissue:  Brain.
References:  56,97
Intestinal smooth muscle contraction, intestinal mobility
Species:  Mouse
Tissue:  Intestinal smooth muscle
References:  93
Physiological Consequences of Altering Gene Expression Click here for help
Disruption of protein kinase A phosphorylation leads to reduced channel activation by isoproterenol and to impaired cardiac function in vivo (reduced exercise capacity, cardiac hypertrophy)
Species:  Mouse
Tissue:  Cardiac myocytes
Technique:  Homologous recombination; mutant mice with impaired protein kinase A phosphorylation (S1700A/T1704A)
References:  23
Cardiac hypertrophy, dilated cardiomyopathy, heart failure
Species:  Mouse
Tissue:  Cardiac myocytes
Technique:  Homologous recombination: reduced expression of Cav1.2 in mouse hearts in various mouse models
References:  10,20,24,28
Hypertrophy and heart failure develop with increasing age. Premature deaths begin at 200 days of age.
Species:  Mouse
Tissue:  Haert
Technique: 
References:  102
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cacna1ctm1Jst Cacna1ctm1Jst/Cacna1ctm1Jst
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:103013  MP:0002206 abnormal CNS synaptic transmission PMID: 15146240 
Cacna1ctm1Hfm Cacna1ctm1Hfm/Cacna1ctm1Hfm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:103013  MP:0002085 abnormal embryonic tissue morphology PMID: 10973973 
Cacna1ctm2Hfm Cacna1ctm2Hfm/Cacna1ctm2Hfm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:103013  MP:0002085 abnormal embryonic tissue morphology PMID: 10973973 
Cacna1ctm1.1Knt Cacna1ctm1.1Knt/Cacna1ctm1.1Knt
involves: 129 * C57BL/6J
MGI:103013  MP:0001449 abnormal learning/ memory PMID: 20190743 
Cacna1ctm1Jst Cacna1ctm1Jst/Cacna1ctm1Jst
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:103013  MP:0002066 abnormal motor capabilities/coordination/movement PMID: 15146240 
Cacna1ctm1Jst Cacna1ctm1Jst/Cacna1ctm1Jst
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:103013  MP:0004215 abnormal myocardial fiber physiology PMID: 15146240 
Cacna1ctm1Jst Cacna1ctm1Jst/Cacna1ctm1Jst
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:103013  MP:0003633 abnormal nervous system physiology PMID: 15146240 
Cacna1ctm3Hfm|Tg(Ins2-cre)25Mgn Cacna1ctm3Hfm/Cacna1ctm3Hfm,Tg(Ins2-cre)25Mgn/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA
MGI:103013  MGI:2176225  MP:0003562 abnormal pancreatic beta cell physiology PMID: 12881419 
Cacna1ctm1Jst Cacna1ctm1Jst/Cacna1ctm1Jst
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:103013  MP:0002573 behavioral despair PMID: 15146240 
Cacna1ctm3Hfm|Tg(Ins2-cre)25Mgn Cacna1ctm3Hfm/Cacna1ctm3Hfm,Tg(Ins2-cre)25Mgn/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA
MGI:103013  MGI:2176225  MP:0002727 decreased circulating insulin level PMID: 12881419 
Cacna1ctm3Hfm|Tg(Ins2-cre)25Mgn Cacna1ctm3Hfm/Cacna1ctm3Hfm,Tg(Ins2-cre)25Mgn/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA
MGI:103013  MGI:2176225  MP:0003059 decreased insulin secretion PMID: 12881419 
Cacna1c+|Cacna1ctm1Dgen Cacna1ctm1Dgen/Cacna1c+
involves: 129P2/OlaHsd * C57BL/6
MGI:103013  MP:0001402 hypoactivity
Cacna1c+|Cacna1ctm1Dgen Cacna1ctm1Dgen/Cacna1c+
involves: 129P2/OlaHsd * C57BL/6
MGI:103013  MP:0001405 impaired coordination
Cacna1ctm3Hfm|Tg(Ins2-cre)25Mgn Cacna1ctm3Hfm/Cacna1ctm3Hfm,Tg(Ins2-cre)25Mgn/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA
MGI:103013  MGI:2176225  MP:0005293 impaired glucose tolerance PMID: 12881419 
Cacna1ctm1.1Knt Cacna1ctm1.1Knt/Cacna1ctm1.1Knt
involves: 129 * C57BL/6J
MGI:103013  MP:0008531 increased chemical nociceptive threshold PMID: 20190743 
Cacna1ctm3Hfm|Tg(Ins2-cre)25Mgn Cacna1ctm3Hfm/Cacna1ctm3Hfm,Tg(Ins2-cre)25Mgn/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA
MGI:103013  MGI:2176225  MP:0005559 increased circulating glucose level PMID: 12881419 
Cacna1c+|Cacna1ctm1Dgen Cacna1ctm1Dgen/Cacna1c+
involves: 129P2/OlaHsd * C57BL/6
MGI:103013  MP:0002797 increased thigmotaxis
Cacna1ctm1Hfm Cacna1ctm1Hfm/Cacna1ctm1Hfm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:103013  MP:0006208 lethality throughout fetal growth and development PMID: 10973973 
Cacna1ctm2Hfm Cacna1ctm2Hfm/Cacna1ctm2Hfm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:103013  MP:0006208 lethality throughout fetal growth and development PMID: 10973973 
Cacna1ctm1Dgen Cacna1ctm1Dgen/Cacna1ctm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:103013  MP:0002082 postnatal lethality
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Angina pectoris
Drugs: 
Side effects:  Hypotension, edema, constipation, bradycardia, AV-block.
Therapeutic use:  Prophylaxis and treatment.
References:  70
Disease:  Arterial hypertension
Drugs: 
Side effects:  Hypotension, edema, constipation, bradycardia, AV-block.
Therapeutic use:  Treatment of hypertension (first-line option).
References:  1,16
Disease:  Brugada syndrome 3; BRGDA3
Synonyms: Brugada syndrome [Orphanet: ORPHA130] [Disease Ontology: DOID:0050451]
Disease Ontology: DOID:0050451
OMIM: 611875
Orphanet: ORPHA130
Role: 
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
In-frame duplication Human p.E1829_Q1833dup c.5485_5499 dup15 see NM_000719 12
Missense Human A39V see NM_000719 2,12,25
Missense Human G490R see NM_000719 2,12,25
Missense Human N547S see NM_000719 2,12,25
Missense Human R858H see NM_000719 2,12,25
Missense Human E1115K see NM_000719 2,12,25
Missense Human C1837Y see NM_000719 2,12,25
Missense Human C1855Y see NM_001167625 2,12,25
Missense Human R1880Q see NM_000719 2,12,25
Missense Human R1970Q see NM_000719 2,12,25
Missense Human V2014I see NM_000719 2,12,25
Missense Human D2130N see NM_000719 2,12,25
Splice defect Human c.1896G>A see NM_000719. This single nucleotide polymorphism did not induce an amino acid change but may cause a splicing error 25
Disease:  Cardiac arrhythmia
Drugs: 
References:  64,70
Disease:  Early repolarization syndrome
Role: 
References:  12
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
In-frame deletion Human E850del c.2548-550del GAG see NM_000719 12
Disease:  Idiopathic ventricular fibrillation
References:  25
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R858H see NM_000719 25
Disease:  Non syndromic autosomal dominant long QT-syndrome
Role: 
References:  11
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human P857R 11
Disease:  Timothy syndrome
Disease Ontology: DOID:0060173
OMIM: 601005
Orphanet: ORPHA65283
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human G402S 82
Missense Human G406R 83
Missense Human A1473G 27
Gene Expression and Pathophysiology Click here for help
Downregulation in animal models of inflamatory bowel disease.
Tissue or cell type:  Intestinal smooth muscle.
Pathophysiology:  Inflammatory bowel disease.
Species:  Dog
Technique:  Immunoblots and patch clamp electrophysiology.
References: 
SNPs in human CACNA1C gene
Tissue or cell type:  Neurons
Pathophysiology:  Risk for psychiatric disorders, including autism spectrum disorders
Species:  Human
Technique: 
References:  17
Gain of Cav1.2 function mutations in mice
Tissue or cell type:  Neurons
Pathophysiology:  Autistic phenotype
Species:  Mouse
Technique: 
References:  3
Upregulation in reactive astrocytes following brain injury.
Tissue or cell type:  Brain.
Pathophysiology:  Brain injury.
Species:  Rat
Technique:  Immunocytochemistry in the shiverer mouse or kainate-lesioned rat
References:  96
Upregulation in reactive astrocytes around amyloid plaques in mouse Alzheimer models
Tissue or cell type:  Reactive astrocytes
Pathophysiology:  Alzheimer's disease
Species:  Mouse
Technique: 
References:  98
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  Predominant smooth muscle splice variant. The RNA sequence is Z34815 - modified, containing exon combination 1/8/9*/32/delta33. The protein sequence is CAA84346.1 - modified, containing exon combination 1/8/9*/32/delta33. The physiological effect is control of vascular tone (window calcium inward current); pharmacological effect is higher sensitivity to dihydropyridine calcium channel blockers than cardiac splice variants; explains pronounced blood pressure lowering effect of these drugs with only minor cardiodepressant action.
References:  49
Type:  Splice variant
Species:  Human
Description:  Predominant heart muscle splice variant. The RNA sequence is Z34815 - modified, containing exon combination 1a/8a/delta9*/32/33. The protein sequence is CAA84346.1 - modified, containing exon combination 1/8/9*/32/delta33. The physiological effect is a major Cav1.2 isoform involved in cardiac contraction while the pharmacological effect is lower sensitivity to dihydropyridine calcium channel blockers than cardiac splice variants
References:  49
Biologically Significant Variant Comments
Smooth muscle and cardiac splice variants exist which differ in their voltage-dependant inactivation properties [49]. Alterations in the splicing pattern was observed in human smooth muscle within atherosclerotic regions [88].

References

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1. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. (2002) Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA, 288 (23): 2981-97. [PMID:12479763]

2. Antzelevitch C, Pollevick GD, Cordeiro JM, Casis O, Sanguinetti MC, Aizawa Y, Guerchicoff A, Pfeiffer R, Oliva A, Wollnik B et al.. (2007) Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation, 115 (4): 442-9. [PMID:17224476]

3. Bader PL, Faizi M, Kim LH, Owen SF, Tadross MR, Alfa RW, Bett GC, Tsien RW, Rasmusson RL, Shamloo M. (2011) Mouse model of Timothy syndrome recapitulates triad of autistic traits. Proc Natl Acad Sci USA, 108 (37): 15432-7. [PMID:21878566]

4. Badou A, Jha MK, Matza D, Mehal WZ, Freichel M, Flockerzi V, Flavell RA. (2006) Critical role for the beta regulatory subunits of Cav channels in T lymphocyte function. Proc Natl Acad Sci USA, 103 (42): 15529-34. [PMID:17028169]

5. Balijepalli RC, Foell JD, Hall DD, Hell JW, Kamp TJ. (2006) Localization of cardiac L-type Ca(2+) channels to a caveolar macromolecular signaling complex is required for beta(2)-adrenergic regulation. Proc Natl Acad Sci USA, 103 (19): 7500-5. [PMID:16648270]

6. Barg S, Ma X, Eliasson L, Galvanovskis J, Göpel SO, Obermüller S, Platzer J, Renström E, Trus M, Atlas D et al.. (2001) Fast exocytosis with few Ca(2+) channels in insulin-secreting mouse pancreatic B cells. Biophys J, 81 (6): 3308-23. [PMID:11720994]

7. Barrere C, Chinda K, Mesirca P, Aurelie C, Diochot S, Lazdunsk M, Barrere-Lamaire S, Mangoni M, Nargeot J. (2020) Evidence for a selective blockade of Cav1.2 versus Cav1.3 by the mamba toxin calciseptine in the mouse heart. Archives of Cardiovascular Diseases Supplements, 12 (2-4): 259. DOI: 10.1016/j.acvdsp.2020.03.144

8. Bean BP. (1984) Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state. Proc Natl Acad Sci USA, 81 (20): 6388-92. [PMID:6093100]

9. Beuckelmann DJ, Näbauer M, Erdmann E. (1991) Characteristics of calcium-current in isolated human ventricular myocytes from patients with terminal heart failure. J Mol Cell Cardiol, 23 (8): 929-37. [PMID:1658345]

10. Blaich A, Pahlavan S, Tian Q, Oberhofer M, Poomvanicha M, Lenhardt P, Domes K, Wegener JW, Moosmang S, Ruppenthal S et al.. (2012) Mutation of the calmodulin binding motif IQ of the L-type Ca(v)1.2 Ca2+ channel to EQ induces dilated cardiomyopathy and death. J Biol Chem, 287 (27): 22616-25. [PMID:22589547]

11. Boczek NJ, Best JM, Tester DJ, Giudicessi JR, Middha S, Evans JM, Kamp TJ, Ackerman MJ. (2013) Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long QT syndrome. Circ Cardiovasc Genet, 6 (3): 279-89. [PMID:23677916]

12. Burashnikov E, Pfeiffer R, Barajas-Martinez H, Delpón E, Hu D, Desai M, Borggrefe M, Häissaguerre M, Kanter R, Pollevick GD et al.. (2010) Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death. Heart Rhythm, 7 (12): 1872-82. [PMID:20817017]

13. Bénitah JP, Bailly P, D'Agrosa MC, Da Ponte JP, Delgado C, Lorente P. (1992) Slow inward current in single cells isolated from adult human ventricles. Pflugers Arch, 421 (2-3): 176-87. [PMID:1356263]

14. Cannell MB, Cheng H, Lederer WJ. (1995) The control of calcium release in heart muscle. Science, 268 (5213): 1045-9. [PMID:7754384]

15. Charnet P, Bourinet E, Dubel SJ, Snutch TP, Nargeot J. (1994) Calcium currents recorded from a neuronal alpha 1C L-type calcium channel in Xenopus oocytes. FEBS Lett, 344 (1): 87-90. [PMID:7514140]

16. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL, Jones DW, Materson BJ, Oparil S, Wright Jr JT et al.. (2003) Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension, 42 (6): 1206-52. [PMID:14656957]

17. Cross-Disorder Group of the Psychiatric Genomics Consortium, Genetic Risk Outcome of Psychosis (GROUP) Consortium. (2013) Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet, 381 (9875): 1371-9. [PMID:23453885]

18. Davare MA, Dong F, Rubin CS, Hell JW. (1999) The A-kinase anchor protein MAP2B and cAMP-dependent protein kinase are associated with class C L-type calcium channels in neurons. J Biol Chem, 274 (42): 30280-7. [PMID:10514522]

19. de Weille JR, Schweitz H, Maes P, Tartar A, Lazdunski M. (1991) Calciseptine, a peptide isolated from black mamba venom, is a specific blocker of the L-type calcium channel. Proc Natl Acad Sci U S A, 88 (6): 2437-40. [PMID:1848702]

20. Domes K, Ding J, Lemke T, Blaich A, Wegener JW, Brandmayr J, Moosmang S, Hofmann F. (2011) Truncation of murine CaV1.2 at Asp-1904 results in heart failure after birth. J Biol Chem, 286 (39): 33863-71. [PMID:21832054]

21. Foell JD, Balijepalli RC, Delisle BP, Yunker AM, Robia SL, Walker JW, McEnery MW, January CT, Kamp TJ. (2004) Molecular heterogeneity of calcium channel beta-subunits in canine and human heart: evidence for differential subcellular localization. Physiol Genomics, 17 (2): 183-200. [PMID:14762176]

22. Fowler MR, Colotti G, Chiancone E, Smith GL, Fearon IM. (2008) Sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit in rabbits. Exp Physiol, 93 (12): 1233-8. [PMID:18603601]

23. Fu Y, Westenbroek RE, Scheuer T, Catterall WA. (2013) Phosphorylation sites required for regulation of cardiac calcium channels in the fight-or-flight response. Proc Natl Acad Sci USA, 110 (48): 19621-6. [PMID:24218620]

24. Fu Y, Westenbroek RE, Yu FH, Clark 3rd JP, Marshall MR, Scheuer T, Catterall WA. (2011) Deletion of the distal C terminus of CaV1.2 channels leads to loss of beta-adrenergic regulation and heart failure in vivo. J Biol Chem, 286 (14): 12617-26. [PMID:21216955]

25. Fukuyama M, Ohno S, Wang Q, Kimura H, Makiyama T, Itoh H, Ito M, Horie M. (2013) L-type calcium channel mutations in Japanese patients with inherited arrhythmias. Circ J, 77 (7): 1799-806. [PMID:23575362]

26. Furukawa T, Miura R, Honda M, Kamiya N, Mori Y, Takeshita S, Isshiki T, Nukada T. (2004) Identification of R(-)-isomer of efonidipine as a selective blocker of T-type Ca2+ channels. Br J Pharmacol, 143 (8): 1050-7. [PMID:15545287]

27. Gillis J, Burashnikov E, Antzelevitch C, Blaser S, Gross G, Turner L, Babul-Hirji R, Chitayat D. (2012) Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome. Am J Med Genet A, 158A (1): 182-7. [PMID:22106044]

28. Goonasekera SA, Hammer K, Auger-Messier M, Bodi I, Chen X, Zhang H, Reiken S, Elrod JW, Correll RN, York AJ et al.. (2012) Decreased cardiac L-type Ca²⁺ channel activity induces hypertrophy and heart failure in mice. J Clin Invest, 122 (1): 280-90. [PMID:22133878]

29. Gómez AM, Valdivia HH, Cheng H, Lederer MR, Santana LF, Cannell MB, McCune SA, Altschuld RA, Lederer WJ. (1997) Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure. Science, 276 (5313): 800-6. [PMID:9115206]

30. Haase H, Kresse A, Hohaus A, Schulte HD, Maier M, Osterziel KJ, Lange PE, Morano I. (1996) Expression of calcium channel subunits in the normal and diseased human myocardium. J Mol Med, 74 (2): 99-104. [PMID:8820405]

31. Hall DD, Dai S, Tseng PY, Malik Z, Nguyen M, Matt L, Schnizler K, Shephard A, Mohapatra DP, Tsuruta F et al.. (2013) Competition between α-actinin and Ca²⁺-calmodulin controls surface retention of the L-type Ca²⁺ channel Ca(V)1.2. Neuron, 78 (3): 483-97. [PMID:23664615]

32. Hall DD, Feekes JA, Arachchige Don AS, Shi M, Hamid J, Chen L, Strack S, Zamponi GW, Horne MC, Hell JW. (2006) Binding of protein phosphatase 2A to the L-type calcium channel Cav1.2 next to Ser1928, its main PKA site, is critical for Ser1928 dephosphorylation. Biochemistry, 45 (10): 3448-59. [PMID:16519540]

33. Helton TD, Xu W, Lipscombe D. (2005) Neuronal L-type calcium channels open quickly and are inhibited slowly. J Neurosci, 25 (44): 10247-51. [PMID:16267232]

34. Hess P, Lansman JB, Tsien RW. (1986) Calcium channel selectivity for divalent and monovalent cations. Voltage and concentration dependence of single channel current in ventricular heart cells. J Gen Physiol, 88 (3): 293-319. [PMID:2428919]

35. Hobai IA, Bates JA, Howarth FC, Levi AJ. (1997) Inhibition by external Cd2+ of Na/Ca exchange and L-type Ca channel in rabbit ventricular myocytes. Am J Physiol, 272 (5 Pt 2): H2164-72. [PMID:9176282]

36. Hockerman GH, Johnson BD, Scheuer T, Catterall WA. (1995) Molecular determinants of high affinity phenylalkylamine block of L-type calcium channels. J Biol Chem, 270 (38): 22119-22. [PMID:7673189]

37. Hong TT, Smyth JW, Gao D, Chu KY, Vogan JM, Fong TS, Jensen BC, Colecraft HM, Shaw RM. (2010) BIN1 localizes the L-type calcium channel to cardiac T-tubules. PLoS Biol, 8 (2): e1000312. [PMID:20169111]

38. Hughes AD, Wijetunge S. (1993) The action of amlodipine on voltage-operated calcium channels in vascular smooth muscle. Br J Pharmacol, 109 (1): 120-5. [PMID:8388295]

39. Jeon D, Kim S, Chetana M, Jo D, Ruley HE, Lin SY, Rabah D, Kinet JP, Shin HS. (2010) Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC. Nat Neurosci, 13 (4): 482-8. [PMID:20190743]

40. Johnson BD, Hockerman GH, Scheuer T, Catterall WA. (1996) Distinct effects of mutations in transmembrane segment IVS6 on block of L-type calcium channels by structurally similar phenylalkylamines. Mol Pharmacol, 50 (5): 1388-400. [PMID:8913371]

41. Kanaya S, Katzung BG. (1984) Effects of diltiazem on transmembrane potential and current of right ventricular papillary muscle of ferrets. J Pharmacol Exp Ther, 228 (1): 245-51. [PMID:6694106]

42. Kang J, Chen XL, Ji J, Lei Q, Rampe D. (2012) Ca²⁺ channel activators reveal differential L-type Ca²⁺ channel pharmacology between native and stem cell-derived cardiomyocytes. J Pharmacol Exp Ther, 341 (2): 510-7. [PMID:22353878]

43. Klugbauer N, Marais E, Hofmann F. (2003) Calcium channel alpha2delta subunits: differential expression, function, and drug binding. J Bioenerg Biomembr, 35 (6): 639-47. [PMID:15000524]

44. Langwieser N, Christel CJ, Kleppisch T, Hofmann F, Wotjak CT, Moosmang S. (2010) Homeostatic switch in hebbian plasticity and fear learning after sustained loss of Cav1.2 calcium channels. J Neurosci, 30 (25): 8367-75. [PMID:20573883]

45. Lee AS, Ra S, Rajadhyaksha AM, Britt JK, De Jesus-Cortes H, Gonzales KL, Lee A, Moosmang S, Hofmann F, Pieper AA et al.. (2012) Forebrain elimination of cacna1c mediates anxiety-like behavior in mice. Mol Psychiatry, 17 (11): 1054-5. [PMID:22665262]

46. Lee TS, Karl R, Moosmang S, Lenhardt P, Klugbauer N, Hofmann F, Kleppisch T, Welling A. (2006) Calmodulin kinase II is involved in voltage-dependent facilitation of the L-type Cav1.2 calcium channel: Identification of the phosphorylation sites. J Biol Chem, 281 (35): 25560-7. [PMID:16820363]

47. Leroy J, Richter W, Mika D, Castro LR, Abi-Gerges A, Xie M, Scheitrum C, Lefebvre F, Schittl J, Mateo P et al.. (2011) Phosphodiesterase 4B in the cardiac L-type Ca²⁺ channel complex regulates Ca²⁺ current and protects against ventricular arrhythmias in mice. J Clin Invest, 121 (7): 2651-61. [PMID:21670503]

48. Li GR, Yang B, Feng J, Bosch RF, Carrier M, Nattel S. (1999) Transmembrane ICa contributes to rate-dependent changes of action potentials in human ventricular myocytes. Am J Physiol, 276 (1): H98-H106. [PMID:9887022]

49. Liao P, Yu D, Li G, Yong TF, Soon JL, Chua YL, Soong TW. (2007) A smooth muscle Cav1.2 calcium channel splice variant underlies hyperpolarized window current and enhanced state-dependent inhibition by nifedipine. J Biol Chem, 282 (48): 35133-42. [PMID:17916557]

50. Liu G, Papa A, Katchman AN, Zakharov SI, Roybal D, Hennessey JA, Kushner J, Yang L, Chen BX, Kushnir A et al.. (2020) Mechanism of adrenergic CaV1.2 stimulation revealed by proximity proteomics. Nature, 577 (7792): 695-700. [PMID:31969708]

51. Liu L, Gonzalez PK, Barrett CF, Rittenhouse AR. (2003) The calcium channel ligand FPL 64176 enhances L-type but inhibits N-type neuronal calcium currents. Neuropharmacology, 45 (2): 281-92. [PMID:12842134]

52. Ludwig A, Flockerzi V, Hofmann F. (1997) Regional expression and cellular localization of the alpha1 and beta subunit of high voltage-activated calcium channels in rat brain. J Neurosci, 17 (4): 1339-49. [PMID:9006977]

53. Magyar J, Iost N, Körtvély A, Bányász T, Virág L, Szigligeti P, Varró A, Opincariu M, Szécsi J, Papp JG et al.. (2000) Effects of endothelin-1 on calcium and potassium currents in undiseased human ventricular myocytes. Pflugers Arch, 441 (1): 144-9. [PMID:11205054]

54. Martin RL, Lee JH, Cribbs LL, Perez-Reyes E, Hanck DA. (2000) Mibefradil block of cloned T-type calcium channels. J Pharmacol Exp Ther, 295 (1): 302-8. [PMID:10991994]

55. Mewes T, Ravens U. (1994) L-type calcium currents of human myocytes from ventricle of non-failing and failing hearts and from atrium. J Mol Cell Cardiol, 26 (10): 1307-20. [PMID:7869391]

56. Moosmang S, Haider N, Klugbauer N, Adelsberger H, Langwieser N, Müller J, Stiess M, Marais E, Schulla V, Lacinova L et al.. (2005) Role of hippocampal Cav1.2 Ca2+ channels in NMDA receptor-independent synaptic plasticity and spatial memory. J Neurosci, 25 (43): 9883-92. [PMID:16251435]

57. Moosmang S, Schulla V, Welling A, Feil R, Feil S, Wegener JW, Hofmann F, Klugbauer N. (2003) Dominant role of smooth muscle L-type calcium channel Cav1.2 for blood pressure regulation. EMBO J, 22 (22): 6027-34. [PMID:14609949]

58. Nokin P, Clinet M, Beaufort P, Meysmans L, Laruel R, Chatelain P. (1990) SR 33557, a novel calcium entry blocker. II. Interactions with 1,4-dihydropyridine, phenylalkylamine and benzothiazepine binding sites in rat heart sarcolemmal membranes. J Pharmacol Exp Ther, 255 (2): 600-7. [PMID:2147036]

59. Oliveria SF, Dittmer PJ, Youn DH, Dell'Acqua ML, Sather WA. (2012) Localized calcineurin confers Ca2+-dependent inactivation on neuronal L-type Ca2+ channels. J Neurosci, 32 (44): 15328-37. [PMID:23115171]

60. Ortner NJ, Bock G, Dougalis A, Kharitonova M, Duda J, Hess S, Tuluc P, Pomberger T, Stefanova N, Pitterl F et al.. (2017) Lower Affinity of Isradipine for L-Type Ca2+ Channels during Substantia Nigra Dopamine Neuron-Like Activity: Implications for Neuroprotection in Parkinson's Disease. J Neurosci, 37 (28): 6761-6777. [PMID:28592699]

61. Pang C, Crump SM, Jin L, Correll RN, Finlin BS, Satin J, Andres DA. (2010) Rem GTPase interacts with the proximal CaV1.2 C-terminus and modulates calcium-dependent channel inactivation. Channels (Austin), 4 (3): 192-202. [PMID:20458179]

62. Papanayotou C, De Almeida I, Liao P, Oliveira NM, Lu SQ, Kougioumtzidou E, Zhu L, Shaw A, Sheng G, Streit A et al.. (2013) Calfacilitin is a calcium channel modulator essential for initiation of neural plate development. Nat Commun, 4: 1837. [PMID:23673622]

63. Park CY, Shcheglovitov A, Dolmetsch R. (2010) The CRAC channel activator STIM1 binds and inhibits L-type voltage-gated calcium channels. Science, 330 (6000): 101-5. [PMID:20929812]

64. Patten M, Maas R, Bauer P, Lüderitz B, Sonntag F, Dluzniewski M, Hatala R, Opolski G, Müller HW, Meinertz T et al.. (2004) Suppression of paroxysmal atrial tachyarrhythmias--results of the SOPAT trial. Eur Heart J, 25 (16): 1395-404. [PMID:15321697]

65. Pelzmann B, Schaffer P, Bernhart E, Lang P, Mächler H, Rigler B, Koidl B. (1998) L-type calcium current in human ventricular myocytes at a physiological temperature from children with tetralogy of Fallot. Cardiovasc Res, 38 (2): 424-32. [PMID:9709403]

66. 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]

67. Peterson BZ, DeMaria CD, Adelman JP, Yue DT. (1999) Calmodulin is the Ca2+ sensor for Ca2+ -dependent inactivation of L-type calcium channels. Neuron, 22 (3): 549-58. [PMID:10197534]

68. Pignier C, Potreau D. (2000) Characterization of nifedipine-resistant calcium current in neonatal rat ventricular cardiomyocytes. Am J Physiol Heart Circ Physiol, 279 (5): H2259-68. [PMID:11045961]

69. Pitt GS. (2007) Calmodulin and CaMKII as molecular switches for cardiac ion channels. Cardiovasc Res, 73 (4): 641-7. [PMID:17137569]

70. Poole-Wilson PA, Lubsen J, Kirwan BA, van Dalen FJ, Wagener G, Danchin N, Just H, Fox KA, Pocock SJ, Clayton TC et al.. (2004) Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial. Lancet, 364 (9437): 849-57. [PMID:15351192]

71. Pérez-Vizcaíno F, Tamargo J, Hof RP, Rüegg UT. (1993) Vascular selectivity of seven prototype calcium antagonists: a study at the single cell level. J Cardiovasc Pharmacol, 22 (5): 768-75. [PMID:7506331]

72. Qin N, Yagel S, Momplaisir ML, Codd EE, D'Andrea MR. (2002) Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit. Mol Pharmacol, 62 (3): 485-96. [PMID:12181424]

73. Ramachandran KV, Hennessey JA, Barnett AS, Yin X, Stadt HA, Foster E, Shah RA, Yazawa M, Dolmetsch RE, Kirby ML et al.. (2013) Calcium influx through L-type CaV1.2 Ca2+ channels regulates mandibular development. J Clin Invest, 123 (4): 1638-46. [PMID:23549079]

74. Robert V, Triffaux E, Paulet PE, Guéry JC, Pelletier L, Savignac M. (2014) Protein kinase C-dependent activation of CaV1.2 channels selectively controls human TH2-lymphocyte functions. J Allergy Clin Immunol, 133 (4): 1175-83. [PMID:24365142]

75. Rosa N, Triffaux E, Robert V, Mars M, Klein M, Bouchaud G, Canivet A, Magnan A, Guéry JC, Pelletier L et al.. (2018) The β and α2δ auxiliary subunits of voltage-gated calcium channel 1 (Cav1) are required for TH2 lymphocyte function and acute allergic airway inflammation. J Allergy Clin Immunol, 142 (3): 892-903.e8. [PMID:29129580]

76. Schulla V, Renström E, Feil R, Feil S, Franklin I, Gjinovci A, Jing XJ, Laux D, Lundquist I, Magnuson MA et al.. (2003) Impaired insulin secretion and glucose tolerance in beta cell-selective Ca(v)1.2 Ca2+ channel null mice. EMBO J, 22 (15): 3844-54. [PMID:12881419]

77. Schultz D, Mikala G, Yatani A, Engle DB, Iles DE, Segers B, Sinke RJ, Weghuis DO, Klöckner U, Wakamori M et al.. (1993) Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart. Proc Natl Acad Sci USA, 90 (13): 6228-32. [PMID:8392192]

78. Schwinger RH, Hoischen S, Reuter H, Hullin R. (1999) Regional expression and functional characterization of the L-type Ca2+-channel in myocardium from patients with end-stage heart failure and in non-failing human hearts. J Mol Cell Cardiol, 31 (1): 283-96. [PMID:10072735]

79. Seisenberger C, Specht V, Welling A, Platzer J, Pfeifer A, Kühbandner S, Striessnig J, Klugbauer N, Feil R, Hofmann F. (2000) Functional embryonic cardiomyocytes after disruption of the L-type alpha1C (Cav1.2) calcium channel gene in the mouse. J Biol Chem, 275 (50): 39193-9. [PMID:10973973]

80. Sinnegger-Brauns MJ, Hetzenauer A, Huber IG, Renström E, Wietzorrek G, Berjukov S, Cavalli M, Walter D, Koschak A, Waldschütz R et al.. (2004) Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca 2+ channels. J Clin Invest, 113 (10): 1430-9. [PMID:15146240]

81. Soldatov NM, Zühlke RD, Bouron A, Reuter H. (1997) Molecular structures involved in L-type calcium channel inactivation. Role of the carboxyl-terminal region encoded by exons 40-42 in alpha1C subunit in the kinetics and Ca2+ dependence of inactivation. J Biol Chem, 272 (6): 3560-6. [PMID:9013606]

82. Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH, Sanguinetti MC, Keating MT. (2005) Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci USA, 102 (23): 8089-8096; discussion 8086-8088. [PMID:15863612]

83. Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, Napolitano C, Schwartz PJ, Joseph RM, Condouris K et al.. (2004) Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell, 119 (1): 19-31. [PMID:15454078]

84. Stokes L, Gordon J, Grafton G. (2004) Non-voltage-gated L-type Ca2+ channels in human T cells: pharmacology and molecular characterization of the major alpha pore-forming and auxiliary beta-subunits. J Biol Chem, 279 (19): 19566-73. [PMID:14981074]

85. Takahashi Y, Jeong SY, Ogata K, Goto J, Hashida H, Isahara K, Uchiyama Y, Kanazawa I. (2003) Human skeletal muscle calcium channel alpha1S is expressed in the basal ganglia: distinctive expression pattern among L-type Ca2+ channels. Neurosci Res, 45 (1): 129-37. [PMID:12507731]

86. Thomsen MB, Wang C, Ozgen N, Wang HG, Rosen MR, Pitt GS. (2009) Accessory subunit KChIP2 modulates the cardiac L-type calcium current. Circ Res, 104 (12): 1382-9. [PMID:19461043]

87. Tippens AL, Lee A. (2007) Caldendrin, a neuron-specific modulator of Cav/1.2 (L-type) Ca2+ channels. J Biol Chem, 282 (11): 8464-73. [PMID:17224447]

88. Tiwari S, Zhang Y, Heller J, Abernethy DR, Soldatov NM. (2006) Atherosclerosis-related molecular alteration of the human CaV1.2 calcium channel alpha1C subunit. Proc Natl Acad Sci USA, 103 (45): 17024-9. [PMID:17071743]

89. Vaeth M, Feske S. (2018) Ion channelopathies of the immune system. Curr Opin Immunol, 52: 39-50. [PMID:29635109]

90. Wang X, Gao G, Guo K, Yarotskyy V, Huang C, Elmslie KS, Peterson BZ. (2010) Phospholemman modulates the gating of cardiac L-type calcium channels. Biophys J, 98 (7): 1149-59. [PMID:20371314]

91. Wang Y, Deng X, Mancarella S, Hendron E, Eguchi S, Soboloff J, Tang XD, Gill DL. (2010) The calcium store sensor, STIM1, reciprocally controls Orai and CaV1.2 channels. Science, 330 (6000): 105-9. [PMID:20929813]

92. Watanabe TX, Itahara Y, Kuroda H, Chen YN, Kimura T, Sakakibara S. (1995) Smooth muscle relaxing and hypotensive activities of synthetic calciseptine and the homologous snake venom peptide FS2. Jpn J Pharmacol, 68 (3): 305-13. [PMID:7474554]

93. Wegener JW, Schulla V, Koller A, Klugbauer N, Feil R, Hofmann F. (2006) Control of intestinal motility by the Ca(v)1.2 L-type calcium channel in mice. FASEB J, 20 (8): 1260-2. [PMID:16636102]

94. Wegener JW, Schulla V, Lee TS, Koller A, Feil S, Feil R, Kleppisch T, Klugbauer N, Moosmang S, Welling A et al.. (2004) An essential role of Cav1.2 L-type calcium channel for urinary bladder function. FASEB J, 18 (10): 1159-61. [PMID:15132976]

95. Weick JP, Groth RD, Isaksen AL, Mermelstein PG. (2003) Interactions with PDZ proteins are required for L-type calcium channels to activate cAMP response element-binding protein-dependent gene expression. J Neurosci, 23 (8): 3446-56. [PMID:12716953]

96. Westenbroek RE, Bausch SB, Lin RC, Franck JE, Noebels JL, Catterall WA. (1998) Upregulation of L-type Ca2+ channels in reactive astrocytes after brain injury, hypomyelination, and ischemia. J Neurosci, 18 (7): 2321-34. [PMID:9502793]

97. White JA, McKinney BC, John MC, Powers PA, Kamp TJ, Murphy GG. (2008) Conditional forebrain deletion of the L-type calcium channel Ca V 1.2 disrupts remote spatial memories in mice. Learn Mem, 15 (1): 1-5. [PMID:18174367]

98. Willis M, Kaufmann WA, Wietzorrek G, Hutter-Paier B, Moosmang S, Humpel C, Hofmann F, Windisch M, Knaus HG, Marksteiner J. (2010) L-type calcium channel CaV 1.2 in transgenic mice overexpressing human AbetaPP751 with the London (V717I) and Swedish (K670M/N671L) mutations. J Alzheimers Dis, 20 (4): 1167-80. [PMID:20413896]

99. Wiśniowska B, Mendyk A, Fijorek K, Glinka A, Polak S. (2012) Predictive model for L-type channel inhibition: multichannel block in QT prolongation risk assessment. J Appl Toxicol, 32 (10): 858-66. [PMID:22761000]

100. Xu H, Ginsburg KS, Hall DD, Zimmermann M, Stein IS, Zhang M, Tandan S, Hill JA, Horne MC, Bers D et al.. (2010) Targeting of protein phosphatases PP2A and PP2B to the C-terminus of the L-type calcium channel Ca v1.2. Biochemistry, 49 (48): 10298-307. [PMID:21053940]

101. Xu W, Lipscombe D. (2001) Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. J Neurosci, 21 (16): 5944-51. [PMID:11487617]

102. Yang L, Dai DF, Yuan C, Westenbroek RE, Yu H, West N, de la Iglesia HO, Catterall WA. (2016) Loss of β-adrenergic-stimulated phosphorylation of CaV1.2 channels on Ser1700 leads to heart failure. Proc Natl Acad Sci U S A, 113 (49): E7976-E7985. [PMID:27864509]

103. Yang T, Puckerin A, Colecraft HM. (2012) Distinct RGK GTPases differentially use α1- and auxiliary β-binding-dependent mechanisms to inhibit CaV1.2/CaV2.2 channels. PLoS ONE, 7 (5): e37079. [PMID:22590648]

104. Zamponi GW. (2003) Calmodulin lobotomized: novel insights into calcium regulation of voltage-gated calcium channels. Neuron, 39 (6): 879-81. [PMID:12971887]

105. Zhang J, Berra-Romani R, Sinnegger-Brauns MJ, Striessnig J, Blaustein MP, Matteson DR. (2007) Role of Cav1.2 L-type Ca2+ channels in vascular tone: effects of nifedipine and Mg2+. Am J Physiol Heart Circ Physiol, 292 (1): H415-25. [PMID:16980345]

106. Zheng W, Rampe D, Triggle DJ. (1991) Pharmacological, radioligand binding, and electrophysiological characteristics of FPL 64176, a novel nondihydropyridine Ca2+ channel activator, in cardiac and vascular preparations. Mol Pharmacol, 40 (5): 734-41. [PMID:1719369]

107. Zühlke RD, Pitt GS, Deisseroth K, Tsien RW, Reuter H. (1999) Calmodulin supports both inactivation and facilitation of L-type calcium channels. Nature, 399 (6732): 159-62. [PMID:10335846]

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