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Cav1.2

Family: Voltage-gated calcium channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Ion Selectivity and Conductance
Voltage Dependence
Activators
Gating Inhibitors
Pore Blockers
Tissue Distribution
Functional Assays
Physiological Functions
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Gene Expression and Pathophysiology
Biologically Significant Variants
References
Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 24 0 2138 12p13.3 CACNA1C calcium channel, voltage-dependent, L type, alpha 1C subunit
Mouse 24 0 2169 6 F1 Cacna1c calcium channel, voltage-dependent, L type, alpha 1C subunit
Rat 24 0 2170 4q42 Cacna1c calcium channel, voltage-dependent, L type, alpha 1C subunit
Previous and Unofficial Names
α1C
cardiac or smooth muscle L-type Ca2+ channel
cardiac or smooth muscle dihydropyridine receptor
Cav1.2
L-type
α1C
cardiac or smooth muscle L
CCHL1A1
CACNL1A1
CACH2
CACN2
TS
LQT8
RATIVS302
Ca channel voltage-dependent L type alpha 1c subunit
Ca channel, voltage-dependent, L type, alpha 1c subunit
L-type calcium channel alpha-1 subunit
RBC
brain class C
calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle
calcium channel, voltage-dependent, alpha 1C subunit
voltage-dependent L-type calcium channel subunit alpha-1C
voltage-gated calcium channel subunit alpha Cav1.2
(alpha)1 subunit
L-type Cav1.2
Database Links
ChEMBL Target 169 (Hs), 10513 (Mm), 10514 (Rn)
DrugBank Target 478 (Hs)
Ensembl ENSG00000151067 (Hs), ENSMUSG00000051331 (Mm), ENSRNOG00000007090 (Rn)
Entrez Gene 775 (Hs), 12288 (Mm), 24239 (Rn)
GeneCards CACNA1C (Hs)
GenitoUrinary Development Molecular Anatomy Project Cacna1c (Mm)
HomoloGene 55484 (Hs)
Human Protein Reference Database 00246 (Hs)
InterPro Q13936 (Hs), Q01815 (Mm), P22002 (Rn)
KEGG Gene hsa:775 (Hs), mmu:12288 (Mm), rno:24239 (Rn)
OMIM 114205 (Hs)
Orphanet Gene ORPHA119140 (Hs)
PharmGKB Gene PA83 (Hs)
PhosphoSitePlus Q13936 (Hs), Q01815 (Mm), P22002 (Rn)
Protein Ontology (PRO) PRO:000002113 (Hs)
RefSeq Nucleotide NM_000719 (Hs), NM_009781 (Mm), NM_012517 (Rn)
RefSeq Protein NP_000710 (Hs), NP_033911 (Mm), NP_036649 (Rn)
TreeFam ENSG00000151067 (Hs), ENSMUSG00000051331 (Mm), ENSRNOG00000007090 (Rn)
UniGene Hs. 118262 (Hs)
UniProt Q13936 (Hs), Q01815 (Mm), P22002 (Rn)
Wikipedia Cav1.2
Voltage-gated calcium channels
Search for 3D structures on the PDB
Search by keyword: Voltage-gated calcium channels Cav1.2 Search by accession number: P22002, Q13936, Q01815
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
β1-4 10
α2δ (isoforms 1-4) 19,35
Other Associated Proteins
Name References
Not determined
Ion Selectivity and Conductance
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:  15
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  0.9 - 47 Xenopus laevis oocyte Human
Inactivation  -14.9 - 47
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -17.6 0.5 – 1.5 14 HEK-293, tsA-201 Mouse
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -6.02 – -0.14 (median: -4.8) 5.2 – 7.1 6,20,24,26,31 Ventricular myocytes. Human
Inactivation  -28.5 – -18.4 (median: -20.4) 9.11 – 21.1 5-6,20,24,26,31
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 - 8 Xenopus laevis oocyte Rat
Inactivation  1.7 30.0 8
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).
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
BAYK 8644 Rn - - 5x10-6 - 8
FPL64176 Rn - - 1x10-6 - 5x10-6 - 22
Gating inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
[3H](+)-isradipine Hs 10.1 – 11.0 pKd - - 38
[3H](+)-isradipine Rn 10.1 pKd - - 41
[3H](-)devapamil Rn 8.21 – 8.36 pKd - - 29,52
[3H](+)-cis-diltiazem Rn 7.15 pKd - - 29
kurtoxin Rn 7.2 pEC50 - -80.0 40
nitrendipine Clf 9.4 pIC50 - -80.0 – 30.0 4
nifedipine Rn 7.66 pIC50 - -80.0 33
(+)-isradipine Mm 7.5 pIC50 - -80.0 41
nifedipine Hs 7.0 – 8.0 pIC50 - -90.0 21
nisoldipine Mm 7.0 – 8.0 pIC50 - -80.0 39
(-)-devapamil Rn 7.3 pIC50 - 10.0 17-18
nisoldipine Hs 7.1 pIC50 - -80.0 44
nimodipine Oc 6.8 pIC50 - -80.0 50
nitrendipine Oc 6.0 pIC50 - -80.0 50
verapamil Rn 5.3 – 6.5 pIC50 - -60.0 – 10.0 18
View species-specific gating inhibitor tables
Gating Inhibitor Comments
Inhibition by dihydropyridines (e.g. nifedipine; [21,33]) is voltage-dependent with a higher apparent affinity at more depolarised potentials; phenylalkylamines (like devapamil; [18]) exhibit strong use-dependence with a higher apparent affinity at higher stimalation frequencies.
Pore Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
Pb2+ Hs 6.4 pIC50 - -70.0 32
Cd2+ Oc 5.7 – 6.0 pIC50 - -80.0 16
mibefradil Hs 4.9 pIC50 - -110.0 25
(-)-(R)-efonidipine Rn 2.0 – 3.5 pIC50 - -100.0 – -60.0 11
View species-specific pore blocker tables

Explore drug-target interactions for this set of compounds using iPHACE

Tissue Distribution
Lymphocytes
Species:  Human
Technique:  RT-PCR, Western blotting.
References:  45
Heart, brain, prostate, bladder,uterus ,stomach, colon, small intestive, placenta, adrenal gland, spinal cord.
Species:  Human
Technique:  Northern Blot
References:  13,37,44
Brain (cortex, pallidum, putamen, hippocampus, caudate nucleas, substantia nigra, cerebellar cortex, dentate nucleus, spinal cord, dorsal root ganglia).
Species:  Human
Technique:  RT-PCR
References:  46
Lymphocytes
Species:  Mouse
Technique:  RT-PCR
References:  2
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:  44
Brain (cerebellum, olfactory bulb, hippocampus (dentate gyrus and Ammon's horn) > amygdala, thalamus).
Species:  Rat
Technique:  In situ hybridisation
References:  23
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 [45].
Functional Assays
Calcium imaging.
Species:  Rat
Tissue:  Cardiac myocytes.
Response measured:  Intracellular calcium transients, calcium release.
References:  7,12
Patch-clamp (whole cell currents and single channel recordings), two-electrode voltage-clamp.
Species:  Human
Tissue:  Cardiac myocytes.
Response measured:  L-type currents
References:  5-6,13,20,24,26,31,41
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:  14,39
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:  8,17-18,22
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:  37,42,44,47
Patch-clamp (whole cell currents and single channel recordings), two-electrode voltage-clamp.
Species:  Rat
Tissue:  Sympathetic neurons.
Response measured:  L-type current
References:  22
Physiological Functions
Urinary bladder function.
Species:  Mouse
Tissue:  Urinary bladder.
References:  48
Insulin secretion, β-cell L-type calcium currents.
Species:  Mouse
Tissue:  Pancreatic β-cells.
References:  3,36,41
Excitation contraction coupling and muscle contraction in heart and vascular smooth muscle.
Species:  Mouse
Tissue:  Heart and vascular smooth muscle.
References:  28,41,51
Early cardiac development.
Species:  Mouse
Tissue:  Embryonal heart.
References:  39
Hippocampal long-term potentiation and spatial memory.
Species:  Mouse
Tissue:  Brain.
References:  27
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

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
Disease:  Cardiac arrhythmias.
Drugs:  Verapamil, methoxyverapamil, diltiazem.
References:  30,34
Mutations not determined
Disease:  Arterial hypertension.
Drugs:  Nifedipine, amlodipine and other DHPs, verapamil, diltiazem.
Side effects:  Hypotension, edema, constipation, bradycardia, AV-block.
Therapeutic use:  Treatment of hypertension (first-line option).
References:  1,9
Mutations not determined
Disease:  Angina pectoris.
Drugs:  Nifedipine, amlodipine and other DHPs, verapamil, diltiazem.
Side effects:  Hypotension, edema, constipation, bradycardia, AV-block.
Therapeutic use:  Prophylaxis and treatment.
References:  34
Mutations not determined
Disease:  Timothy syndrome
OMIM:  601005
Orphanet:  65283
References: 
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human G406R 44
Missense Human G402S 43
Disease:  Brugada syndrome 3; BRGDA3
OMIM:  611875
Orphanet:  130
References: 
Mutations not determined
Gene Expression and Pathophysiology
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:  49
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: 
Biologically Significant Variant Comments
Smooth muscle and cardiac splice variants exist which differ in their voltage-dependant inactivation properties [21]. Alterations in the splicing pattern was observed in human smooth muscle within atherosclerotic regions [47].

REFERENCES

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2. 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. U.S.A., 103 (42): 15529-34. [PMID:17028169]

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

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21. 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]

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25. 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]

26. 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]

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To cite this database page, please use the following:

William A. Catterall, Edward Perez-Reyes, Terrance P. Snutch, Joerg Striessnig.
Voltage-gated calcium channels: Cav1.2. Last modified on 23/01/2012. Accessed on 20/06/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=5290.


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