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R-type calcium channel

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Protein family

R-type calcium channel

Identifiers

Aliases

External IDs

GeneCards:[1];OMA:- orthologs

Orthologs

Species

Human

Mouse

Entrez


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Ensembl


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UniProt


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RefSeq (mRNA)


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RefSeq (protein)


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Location (UCSC)

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PubMed search

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Wikidata

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TheR-type calcium channel is a type ofvoltage-dependent calcium channel. Like the others of this class, the α₁ subunit forms the pore through which calcium enters the cell and determines most of the channel's properties. This α₁ subunit is also known as thecalcium channel, voltage-dependent, R type, alpha 1E subunit (CACNA1E) orCav_2.3 which in humans is encoded by theCACNA1Egene.^[1]^[2]^[3]They are strongly expressed in cortex, hippocampus, striatum, amygdala and interpeduncular nucleus.^[4]

They are poorly understood, but likeQ-type calcium channels, they appear to be present incerebellar granule cells. They have a high threshold of activation and relatively slow kinetics.

References

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^"Entrez Gene: CACNA1E calcium channel, voltage-dependent, R type, alpha 1E subunit".
^Soong TW, Stea A, Hodson CD, Dubel SJ, Vincent SR, Snutch TP (May 1993). "Structure and functional expression of a member of the low voltage-activated calcium channel family".Science.260 (5111):1133–6.Bibcode:1993Sci...260.1133S.doi:10.1126/science.8388125.PMID 8388125.
^Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (December 2005). "International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels".Pharmacological Reviews.57 (4):411–25.doi:10.1124/pr.57.4.5.PMID 16382099.S2CID 10386627.
^Parajuli LK, Nakajima C, Kulik A, Matsui K, Schneider T, Shigemoto R, Fukazawa Y (September 2012)."Quantitative regional and ultrastructural localization of the Ca(v)2.3 subunit of R-type calcium channel in mouse brain".The Journal of Neuroscience.32 (39):13555–67.doi:10.1523/jneurosci.1142-12.2012.PMC 6621359.PMID 23015445.

McNaughton NC, Green PJ, Randall AD (December 2001). "Inhibition of human alpha1E subunit-mediated ca2+ channels by the antipsychotic agent chlorpromazine".Acta Physiologica Scandinavica.173 (4):401–8.doi:10.1046/j.1365-201X.2001.00914.x.PMID 11903132.
Berrou L, Klein H, Bernatchez G, Parent L (September 2002)."A specific tryptophan in the I-II linker is a key determinant of beta-subunit binding and modulation in Ca(V)2.3 calcium channels".Biophysical Journal.83 (3):1429–42.Bibcode:2002BpJ....83.1429B.doi:10.1016/S0006-3495(02)73914-3.PMC 1302242.PMID 12202369.
Raybaud A, Baspinar EE, Dionne F, Dodier Y, Sauvé R, Parent L (September 2007)."The role of distal S6 hydrophobic residues in the voltage-dependent gating of CaV2.3 channels".The Journal of Biological Chemistry.282 (38):27944–52.doi:10.1074/jbc.M703895200.PMID 17660294.
Toro-Castillo C, Thapliyal A, Gonzalez-Ochoa H, Adams BA, Meza U (January 2007). "Muscarinic modulation of Cav2.3 (R-type) calcium channels is antagonized by RGS3 and RGS3T".American Journal of Physiology. Cell Physiology.292 (1): C573–80.doi:10.1152/ajpcell.00219.2006.PMID 16855219.
Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (December 2005). "International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels".Pharmacological Reviews.57 (4):411–25.doi:10.1124/pr.57.4.5.PMID 16382099.S2CID 10386627.
Kang HW, Moon HJ, Joo SH, Lee JH (December 2007). "Histidine residues in the IS3-IS4 loop are critical for nickel-sensitive inhibition of the Cav2.3 calcium channel".FEBS Letters.581 (30):5774–80.Bibcode:2007FEBSL.581.5774K.doi:10.1016/j.febslet.2007.11.045.PMID 18037383.S2CID 12259094.
Natrajan R, Little SE, Reis-Filho JS, Hing L, Messahel B, Grundy PE, Dome JS, Schneider T, Vujanic GM, Pritchard-Jones K, Jones C (December 2006)."Amplification and overexpression of CACNA1E correlates with relapse in favorable histology Wilms' tumors".Clinical Cancer Research.12 (24):7284–93.doi:10.1158/1078-0432.CCR-06-1567.PMID 17189400.
Holmkvist J, Tojjar D, Almgren P, Lyssenko V, Lindgren CM, Isomaa B, Tuomi T, Berglund G, Renström E, Groop L (December 2007)."Polymorphisms in the gene encoding the voltage-dependent Ca(2+) channel Ca (V)2.3 (CACNA1E) are associated with type 2 diabetes and impaired insulin secretion".Diabetologia.50 (12):2467–75.doi:10.1007/s00125-007-0846-2.PMID 17934712.
Nyholt DR, LaForge KS, Kallela M, Alakurtti K, Anttila V, Färkkilä M, Hämaläinen E, Kaprio J, Kaunisto MA, Heath AC, Montgomery GW, Göbel H, Todt U, Ferrari MD, Launer LJ, Frants RR, Terwindt GM, de Vries B, Verschuren WM, Brand J, Freilinger T, Pfaffenrath V, Straube A, Ballinger DG, Zhan Y, Daly MJ, Cox DR, Dichgans M, van den Maagdenberg AM, Kubisch C, Martin NG, Wessman M, Peltonen L, Palotie A (November 2008)."A high-density association screen of 155 ion transport genes for involvement with common migraine".Human Molecular Genetics.17 (21):3318–31.doi:10.1093/hmg/ddn227.PMC 2566523.PMID 18676988.
Suzuki T, Delgado-Escueta AV, Aguan K, Alonso ME, Shi J, Hara Y, Nishida M, Numata T, Medina MT, Takeuchi T, Morita R, Bai D, Ganesh S, Sugimoto Y, Inazawa J, Bailey JN, Ochoa A, Jara-Prado A, Rasmussen A, Ramos-Peek J, Cordova S, Rubio-Donnadieu F, Inoue Y, Osawa M, Kaneko S, Oguni H, Mori Y, Yamakawa K (August 2004). "Mutations in EFHC1 cause juvenile myoclonic epilepsy".Nature Genetics.36 (8):842–9.doi:10.1038/ng1393.PMID 15258581.S2CID 32916803.
Hainsworth AH, McNaughton NC, Pereverzev A, Schneider T, Randall AD (April 2003). "Actions of sipatrigine, 202W92 and lamotrigine on R-type and T-type Ca2+ channel currents".European Journal of Pharmacology.467 (1–3):77–80.doi:10.1016/S0014-2999(03)01625-X.PMID 12706458.
Kamp MA, Krieger A, Henry M, Hescheler J, Weiergräber M, Schneider T (March 2005). "Presynaptic 'Ca2.3-containing' E-type Ca channels share dual roles during neurotransmitter release".The European Journal of Neuroscience.21 (6):1617–25.doi:10.1111/j.1460-9568.2005.03984.x.PMID 15845089.S2CID 37439621.
Berrou L, Bernatchez G, Parent L (January 2001)."Molecular determinants of inactivation within the I-II linker of alpha1E (CaV2.3) calcium channels".Biophysical Journal.80 (1):215–28.Bibcode:2001BpJ....80..215B.doi:10.1016/S0006-3495(01)76008-0.PMC 1301227.PMID 11159396.
Meza U, Thapliyal A, Bannister RA, Adams BA (January 2007). "Neurokinin 1 receptors trigger overlapping stimulation and inhibition of CaV2.3 (R-type) calcium channels".Molecular Pharmacology.71 (1):284–93.doi:10.1124/mol.106.028530.PMID 17050807.S2CID 3106603.
Bernatchez G, Sauvé R, Parent L (November 2001). "State-dependent inhibition of inactivation-deficient Ca(V)1.2 and Ca(V)2.3 channels by mibefradil".The Journal of Membrane Biology.184 (2):143–59.doi:10.1007/s00232-001-0083-4.PMID 11719851.S2CID 10302141.
Pereverzev A, Leroy J, Krieger A, Malécot CO, Hescheler J, Pfitzer G, Klöckner U, Schneider T (October 2002). "Alternate splicing in the cytosolic II-III loop and the carboxy terminus of human E-type voltage-gated Ca(2+) channels: electrophysiological characterization of isoforms".Molecular and Cellular Neurosciences.21 (2):352–65.doi:10.1006/mcne.2002.1179.PMID 12401453.S2CID 21472619.
Fernandez F, Curtain RP, Colson NJ, Ovcaric M, MacMillan J, Griffiths LR (August 2007)."Association analysis of chromosome 1 migraine candidate genes".BMC Medical Genetics.8: 57.doi:10.1186/1471-2350-8-57.PMC 2034370.PMID 17727731.
Vajna R, Klöckner U, Pereverzev A, Weiergräber M, Chen X, Miljanich G, Klugbauer N, Hescheler J, Perez-Reyes E, Schneider T (February 2001)."Functional coupling between 'R-type' Ca2+ channels and insulin secretion in the insulinoma cell line INS-1".European Journal of Biochemistry.268 (4):1066–75.doi:10.1046/j.1432-1327.2001.01969.x.PMID 11179973.
Muller YL, Hanson RL, Zimmerman C, Harper I, Sutherland J, Kobes S, Knowler WC, Bogardus C, Baier LJ (December 2007)."Variants in the Ca V 2.3 (alpha 1E) subunit of voltage-activated Ca2+ channels are associated with insulin resistance and type 2 diabetes in Pima Indians".Diabetes.56 (12):3089–94.doi:10.2337/db07-0587.PMID 17720895.

External links

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CACNA1E+protein,+human at the U.S. National Library of MedicineMedical Subject Headings (MeSH)
R-Type+Calcium+Channel at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

Membrane transport protein:ion channels (TC 1A)

Ca²⁺:Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3
Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺:Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ
Proton-gated	Amiloride-sensitive cation channel 1 2 3 4
Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺:Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1
Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1
Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18
Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker (gene)

Miscellaneous

Cl⁻:Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B
H⁺:Proton channel	HVCN1
M⁺:CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4
M⁺:TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6
H₂O (+solutes):Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family
Cytoplasm:Gap junction	Connexin A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4 Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

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