Cav1.3
Target has curated data in GtoImmuPdb
Target id: 530
Nomenclature: Cav1.3
Family: Voltage-gated calcium channels
Annotation status:
Annotated and expert reviewed. Please contact us if you can help with updates.
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Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Associated Proteins
- Functional Characteristics
- Ion Selectivity and Conductance
- Voltage Dependence
- Activators
- Gating Inhibitors
- Channel Blockers
- Immunopharmacology Comments
- Immuno Cell Type Associations
- Tissue Distribution
- Functional Assays
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Biologically Significant Variants
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 24 | 4 | 2181 | 3p14.3 | CACNA1D | calcium voltage-gated channel subunit alpha1 D | 29,53 |
| Mouse | 24 | 4 | 2166 | 14 B | Cacna1d | calcium channel, voltage-dependent, L type, alpha 1D subunit | 68 |
| Rat | 24 | 4 | 2203 | 16p16 | Cacna1d | calcium voltage-gated channel subunit alpha1 D | 24,69 |
| Previous and Unofficial Names |
| neuroendocrine L-type Ca2+ channel | α1D | CACH3 | CACN4 | CACNL1A2 | CCHL1A2 | calcium channel alpha-1 subunit | Cchl1a | calcium channel |
| Database Links |
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| ChEMBL Target | CHEMBL4138 (Hs), CHEMBL3988632 (Mm), CHEMBL4132 (Rn) |
| DrugBank Target | Q01668 (Hs) |
| Ensembl Gene | ENSG00000157388 (Hs), ENSMUSG00000015968 (Mm), ENSRNOG00000013147 (Rn) |
| Entrez Gene | 776 (Hs), 12289 (Mm), 29716 (Rn) |
| Human Protein Atlas | ENSG00000157388 (Hs) |
| KEGG Gene | hsa:776 (Hs), mmu:12289 (Mm), rno:29716 (Rn) |
| OMIM | 114206 (Hs) |
| Orphanet | ORPHA327310 (Hs) |
| RefSeq Nucleotide | NM_000720 (Hs), NM_028981 (Mm), NM_017298 (Rn) |
| RefSeq Protein | NP_000711 (Hs), NP_083257 (Mm), NP_058994 (Rn) |
| UniProtKB | Q01668 (Hs), Q99246 (Mm), P27732 (Rn) |
| Wikipedia | CACNA1D (Hs) |
| Associated Proteins |
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| Functional Characteristics |
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| L-type calcium current: moderate-voltage, slow voltage-dependent inactivation, more rapid calcium-dependent inactivation | |
| Ion Selectivity and Conductance |
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| Voltage Dependence |
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| Voltage Dependence Comments | ||||||||||||||||||||||
| Data are given for both Ca2+ and Ba2+ as the charge carrier. V0.5 for activation is higher with Ca2+ as a charge carrier than with Ba2+ (but more negative than for Cav1.2 under identical experimental conditions; [69]). Activation and inactivation parameters differ between different C-terminal splice variants (long and several short forms; [4,31,56,63]). Short forms lack a C-terminal modulatory domain which reduces calcium-dependent inactivation and reduces voltage-sensitivity. Inactivation time course depends on associated β subunit (slower with β2), C-terminal splice variant and on charge carrier (pronounced calcium-induced inactivation with Ca2+; [56]). |
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Download all structure-activity data for this target as a CSV file 
| Activators | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific activator tables | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Activator Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Using rat channels, BAYK 8644 (1μM) shifted the V0.5 towards a more hyperpolarised voltage (-32.2mV to -39.0mV) [69]. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Gating inhibitors
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific gating inhibitor tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Gating Inhibitor Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nitrendipine appears to interact more effectively with L-type calcium channels in smooth muscle cells. We have chosen to tag the drug's interaction with Cav1.3 as the primary drug target, but this does not preclude activity at other additional channels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Channel Blockers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific channel blocker tables | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Channel Blocker Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Verapamil is an example of a dihydropyridine antagonist; Cav1.3 is less sensitive to dihydropyridine antagonists than other members of this family. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Immunopharmacology Comments |
| Cav1.3 and Cav1.4 are involved in CD8+ T cell survival and cytokine production [40]. |
| Cell Type Associations | ||||
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| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| The physiological role of Cav1.3 L-type channels for lymphocyte function is not well established. Additionally, in lymphocytes the presence of Cav1.3 α1 subunit protein has not yet been proven using Cav1.3-α1 deficient mice as negative controls; therefore the specificity of antibody staining remians questionable [9,60]. | ||||||||
| Functional Assays
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| Physiological Functions
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| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| Clinically-Relevant Mutations and Pathophysiology Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Gain of function is shown for several of the mutations associated with aldosterone-producing adrenal adenomas. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biologically Significant Variants
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References
1. Azizan EA, Poulsen H, Tuluc P, Zhou J, Clausen MV, Lieb A, Maniero C, Garg S, Bochukova EG, Zhao W et al.. (2013) Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Nat. Genet., 45 (9): 1055-60. [PMID:23913004]
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. Baig SM, Koschak A, Lieb A, Gebhart M, Dafinger C, Nürnberg G, Ali A, Ahmad I, Sinnegger-Brauns MJ, Brandt N et al.. (2011) Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness. Nat. Neurosci., 14 (1): 77-84. [PMID:21131953]
4. Bock G, Gebhart M, Scharinger A, Jangsangthong W, Busquet P, Poggiani C, Sartori S, Mangoni ME, Sinnegger-Brauns MJ, Herzig S et al.. (2011) Functional properties of a newly identified C-terminal splice variant of Cav1.3 L-type Ca2+ channels. J. Biol. Chem., 286 (49): 42736-48. [PMID:21998310]
5. Brandt A, Khimich D, Moser T. (2005) Few CaV1.3 channels regulate the exocytosis of a synaptic vesicle at the hair cell ribbon synapse. J. Neurosci., 25 (50): 11577-85. [PMID:16354915]
6. Brandt A, Striessnig J, Moser T. (2003) CaV1.3 channels are essential for development and presynaptic activity of cochlear inner hair cells. J. Neurosci., 23 (34): 10832-40. [PMID:14645476]
7. Busquet P, Nguyen NK, Schmid E, Tanimoto N, Seeliger MW, Ben-Yosef T, Mizuno F, Akopian A, Striessnig J, Singewald N. (2010) CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype. Int. J. Neuropsychopharmacol., 13 (4): 499-513. [PMID:19664321]
8. Béguin P, Nagashima K, Gonoi T, Shibasaki T, Takahashi K, Kashima Y, Ozaki N, Geering K, Iwanaga T, Seino S. (2001) Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem. Nature, 411 (6838): 701-6. [PMID:11395774]
9. Cabral MD, Paulet PE, Robert V, Gomes B, Renoud ML, Savignac M, Leclerc C, Moreau M, Lair D, Langelot M et al.. (2010) Knocking down Cav1 calcium channels implicated in Th2 cell activation prevents experimental asthma. Am. J. Respir. Crit. Care Med., 181 (12): 1310-7. [PMID:20167851]
10. Calin-Jageman I, Yu K, Hall RA, Mei L, Lee A. (2007) Erbin enhances voltage-dependent facilitation of Ca(v)1.3 Ca2+ channels through relief of an autoinhibitory domain in the Ca(v)1.3 alpha1 subunit. J. Neurosci., 27 (6): 1374-85. [PMID:17287512]
11. Clark NC, Nagano N, Kuenzi FM, Jarolimek W, Huber I, Walter D, Wietzorrek G, Boyce S, Kullmann DM, Striessnig J, Seabrook GR. (2003) Neurological phenotype and synaptic function in mice lacking the CaV1.3 alpha subunit of neuronal L-type voltage-dependent Ca2+ channels. Neuroscience, 120 (2): 435-42. [PMID:12890513]
12. Cui G, Meyer AC, Calin-Jageman I, Neef J, Haeseleer F, Moser T, Lee A. (2007) Ca2+-binding proteins tune Ca2+-feedback to Cav1.3 channels in mouse auditory hair cells. J. Physiol. (Lond.), 585 (Pt 3): 791-803. [PMID:17947313]
13. Cunha SR, Hund TJ, Hashemi S, Voigt N, Li N, Wright P, Koval O, Li J, Gudmundsson H, Gumina RJ et al.. (2011) Defects in ankyrin-based membrane protein targeting pathways underlie atrial fibrillation. Circulation, 124 (11): 1212-22. [PMID:21859974]
14. Dick IE, Tadross MR, Liang H, Tay LH, Yang W, Yue DT. (2008) A modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels. Nature, 451 (7180): 830-4. [PMID:18235447]
15. Gebhart M, Juhasz-Vedres G, Zuccotti A, Brandt N, Engel J, Trockenbacher A, Kaur G, Obermair GJ, Knipper M, Koschak A et al.. (2010) Modulation of Cav1.3 Ca2+ channel gating by Rab3 interacting molecule. Mol. Cell. Neurosci., 44 (3): 246-59. [PMID:20363327]
16. Giordano TP, Tropea TF, Satpute SS, Sinnegger-Brauns MJ, Striessnig J, Kosofsky BE, Rajadhyaksha AM. (2010) Molecular switch from L-type Ca v 1.3 to Ca v 1.2 Ca2+ channel signaling underlies long-term psychostimulant-induced behavioral and molecular plasticity. J. Neurosci., 30 (50): 17051-62. [PMID:21159975]
17. Grant L, Fuchs P. (2008) Calcium- and calmodulin-dependent inactivation of calcium channels in inner hair cells of the rat cochlea. J. Neurophysiol., 99 (5): 2183-93. [PMID:18322004]
18. Gregory FD, Bryan KE, Pangršič T, Calin-Jageman IE, Moser T, Lee A. (2011) Harmonin inhibits presynaptic Cav1.3 Ca²⁺ channels in mouse inner hair cells. Nat. Neurosci., 14 (9): 1109-11. [PMID:21822269]
19. Gregory FD, Pangrsic T, Calin-Jageman IE, Moser T, Lee A. (2013) Harmonin enhances voltage-dependent facilitation of Cav1.3 channels and synchronous exocytosis in mouse inner hair cells. J. Physiol. (Lond.), 591 (Pt 13): 3253-69. [PMID:23613530]
20. 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]
21. Hibino H, Pironkova R, Onwumere O, Rousset M, Charnet P, Hudspeth AJ, Lesage F. (2003) Direct interaction with a nuclear protein and regulation of gene silencing by a variant of the Ca2+-channel beta 4 subunit. Proc. Natl. Acad. Sci. U.S.A., 100 (1): 307-12. [PMID:12518067]
22. Hirtz JJ, Braun N, Griesemer D, Hannes C, Janz K, Löhrke S, Müller B, Friauf E. (2012) Synaptic refinement of an inhibitory topographic map in the auditory brainstem requires functional Cav1.3 calcium channels. J. Neurosci., 32 (42): 14602-16. [PMID:23077046]
23. Huang H, Yu D, Soong TW. (2013) C-terminal alternative splicing of CaV1.3 channels distinctively modulates their dihydropyridine sensitivity. Mol. Pharmacol., 84 (4): 643-53. [PMID:23924992]
24. Ihara Y, Yamada Y, Fujii Y, Gonoi T, Yano H, Yasuda K, Inagaki N, Seino Y, Seino S. (1995) Molecular diversity and functional characterization of voltage-dependent calcium channels (CACN4) expressed in pancreatic beta-cells. Mol. Endocrinol., 9 (1): 121-30. [PMID:7760845]
25. Jenkins MA, Christel CJ, Jiao Y, Abiria S, Kim KY, Usachev YM, Obermair GJ, Colbran RJ, Lee A. (2010) Ca2+-dependent facilitation of Cav1.3 Ca2+ channels by densin and Ca2+/calmodulin-dependent protein kinase II. J. Neurosci., 30 (15): 5125-35. [PMID:20392935]
26. Kersten FF, van Wijk E, van Reeuwijk J, van der Zwaag B, Märker T, Peters TA, Katsanis N, Wolfrum U, Keunen JE, Roepman R et al.. (2010) Association of whirlin with Cav1.3 (alpha1D) channels in photoreceptors, defining a novel member of the usher protein network. Invest. Ophthalmol. Vis. Sci., 51 (5): 2338-46. [PMID:19959638]
27. Kim S, Yun HM, Baik JH, Chung KC, Nah SY, Rhim H. (2007) Functional interaction of neuronal Cav1.3 L-type calcium channel with ryanodine receptor type 2 in the rat hippocampus. J. Biol. Chem., 282 (45): 32877-89. [PMID:17823125]
28. 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]
29. Koschak A, Reimer D, Huber I, Grabner M, Glossmann H, Engel J, Striessnig J. (2001) alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages. J. Biol. Chem., 276 (25): 22100-6. [PMID:11285265]
30. Koschak A, Reimer D, Walter D, Hoda JC, Heinzle T, Grabner M, Striessnig J. (2003) Cav1.4alpha1 subunits can form slowly inactivating dihydropyridine-sensitive L-type Ca2+ channels lacking Ca2+-dependent inactivation. J. Neurosci., 23 (14): 6041-9. [PMID:12853422]
31. Lieb A, Scharinger A, Sartori S, Sinnegger-Brauns MJ, Striessnig J. (2012) Structural determinants of CaV1.3 L-type calcium channel gating. Channels (Austin), 6 (3): 197-205. [PMID:22760075]
32. Mangoni ME, Couette B, Bourinet E, Platzer J, Reimer D, Striessnig J, Nargeot J. (2003) Functional role of L-type Cav1.3 Ca2+ channels in cardiac pacemaker activity. Proc. Natl. Acad. Sci. U.S.A., 100 (9): 5543-8. [PMID:12700358]
33. Marcantoni A, Vandael DH, Mahapatra S, Carabelli V, Sinnegger-Brauns MJ, Striessnig J, Carbone E. (2010) Loss of Cav1.3 channels reveals the critical role of L-type and BK channel coupling in pacemaking mouse adrenal chromaffin cells. J. Neurosci., 30 (2): 491-504. [PMID:20071512]
34. Marshall MR, Clark 3rd JP, Westenbroek R, Yu FH, Scheuer T, Catterall WA. (2011) Functional roles of a C-terminal signaling complex of CaV1 channels and A-kinase anchoring protein 15 in brain neurons. J. Biol. Chem., 286 (14): 12627-39. [PMID:21224388]
35. McKinney BC, Murphy GG. (2006) The L-Type voltage-gated calcium channel Cav1.3 mediates consolidation, but not extinction, of contextually conditioned fear in mice. Learn. Mem., 13 (5): 584-9. [PMID:17015855]
36. McKinney BC, Sze W, Lee B, Murphy GG. (2009) Impaired long-term potentiation and enhanced neuronal excitability in the amygdala of Ca(V)1.3 knockout mice. Neurobiol Learn Mem, 92 (4): 519-28. [PMID:19595780]
37. Michna M, Knirsch M, Hoda JC, Muenkner S, Langer P, Platzer J, Striessnig J, Engel J. (2003) Cav1.3 (alpha1D) Ca2+ currents in neonatal outer hair cells of mice. J. Physiol. (Lond.), 553 (Pt 3): 747-58. [PMID:14514878]
38. O'Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP, Levy R, Ko A, Lee C, Smith JD et al.. (2012) Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature, 485 (7397): 246-50. [PMID:22495309]
39. Olson PA, Tkatch T, Hernandez-Lopez S, Ulrich S, Ilijic E, Mugnaini E, Zhang H, Bezprozvanny I, Surmeier DJ. (2005) G-protein-coupled receptor modulation of striatal CaV1.3 L-type Ca2+ channels is dependent on a Shank-binding domain. J. Neurosci., 25 (5): 1050-62. [PMID:15689540]
40. Omilusik K, Priatel JJ, Chen X, Wang YT, Xu H, Choi KB, Gopaul R, McIntyre-Smith A, Teh HS, Tan R et al.. (2011) The Ca(v)1.4 calcium channel is a critical regulator of T cell receptor signaling and naive T cell homeostasis. Immunity, 35 (3): 349-60. [PMID:21835646]
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William A. Catterall, Edward Perez-Reyes, Terrance P. Snutch, Jörg Striessnig.
Voltage-gated calcium channels: Cav1.3. Last modified on 06/03/2019. Accessed on 20/05/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=530.
