R-type calcium channel

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GeneCards:

Orthologs

Species

Human

Mouse

Entrez


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UniProt


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The R-type calcium channel is a type of voltage-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 the calcium channel, voltage-dependent, R type, alpha 1E subunit (CACNA1E) or Cav_2.3 which in humans is encoded by the CACNA1E gene.^[1]^[2]^[3] They are strongly expressed in cortex, hippocampus, striatum, amygdala and interpeduncular nucleus.^[4]

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

References

↑ "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. 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". Pharmacol. Rev. 57 (4): 411–25. doi:10.1124/pr.57.4.5. PMID 16382099.
↑ 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". J Neurosci. 32 (39): 13555–67. doi:10.1523/jneurosci.1142-12.2012. PMID 23015445.

McNaughton NC, Green PJ, Randall AD (2001). "Inhibition of human alpha1E subunit-mediated ca2+ channels by the antipsychotic agent chlorpromazine.". Acta Physiol. Scand. 173 (4): 401–8. doi:10.1046/j.1365-201X.2001.00914.x. PMID 11903132.
Berrou L, Klein H, Bernatchez G, Parent L (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". Biophys. J. 83 (3): 1429–42. doi:10.1016/S0006-3495(02)73914-3. PMC 1302242. PMID 12202369.
Raybaud A, Baspinar EE, Dionne F, et al. (2007). "The role of distal S6 hydrophobic residues in the voltage-dependent gating of CaV2.3 channels". J. Biol. Chem. 282 (38): 27944–52. doi:10.1074/jbc.M703895200. PMID 17660294.
Toro-Castillo C, Thapliyal A, Gonzalez-Ochoa H, et al. (2007). "Muscarinic modulation of Cav2.3 (R-type) calcium channels is antagonized by RGS3 and RGS3T". Am. J. Physiol., Cell Physiol. 292 (1): C573–80. doi:10.1152/ajpcell.00219.2006. PMID 16855219.
Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (2005). "International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels". Pharmacol. Rev. 57 (4): 411–25. doi:10.1124/pr.57.4.5. PMID 16382099.
Kang HW, Moon HJ, Joo SH, Lee JH (2007). "Histidine residues in the IS3-IS4 loop are critical for nickel-sensitive inhibition of the Cav2.3 calcium channel". FEBS Lett. 581 (30): 5774–80. doi:10.1016/j.febslet.2007.11.045. PMID 18037383.
Natrajan R, Little SE, Reis-Filho JS, et al. (2006). "Amplification and overexpression of CACNA1E correlates with relapse in favorable histology Wilms' tumors". Clin. Cancer Res. 12 (24): 7284–93. doi:10.1158/1078-0432.CCR-06-1567. PMID 17189400.
Holmkvist J, Tojjar D, Almgren P, et al. (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, et al. (2008). "A high-density association screen of 155 ion transport genes for involvement with common migraine". Hum. Mol. Genet. 17 (21): 3318–31. doi:10.1093/hmg/ddn227. PMC 2566523. PMID 18676988.
Suzuki T, Delgado-Escueta AV, Aguan K, et al. (2004). "Mutations in EFHC1 cause juvenile myoclonic epilepsy". Nat. Genet. 36 (8): 842–9. doi:10.1038/ng1393. PMID 15258581.
Hainsworth AH, McNaughton NC, Pereverzev A, et al. (2003). "Actions of sipatrigine, 202W92 and lamotrigine on R-type and T-type Ca2+ channel currents". Eur. J. Pharmacol. 467 (1–3): 77–80. doi:10.1016/S0014-2999(03)01625-X. PMID 12706458.
Kamp MA, Krieger A, Henry M, et al. (2005). "Presynaptic 'Ca2.3-containing' E-type Ca channels share dual roles during neurotransmitter release". Eur. J. Neurosci. 21 (6): 1617–25. doi:10.1111/j.1460-9568.2005.03984.x. PMID 15845089.
Berrou L, Bernatchez G, Parent L (2001). "Molecular determinants of inactivation within the I-II linker of alpha1E (CaV2.3) calcium channels". Biophys. J. 80 (1): 215–28. doi:10.1016/S0006-3495(01)76008-0. PMC 1301227. PMID 11159396.
Meza U, Thapliyal A, Bannister RA, Adams BA (2007). "Neurokinin 1 receptors trigger overlapping stimulation and inhibition of CaV2.3 (R-type) calcium channels". Mol. Pharmacol. 71 (1): 284–93. doi:10.1124/mol.106.028530. PMID 17050807.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Bernatchez G, Sauvé R, Parent L (2001). "State-dependent inhibition of inactivation-deficient Ca(V)1.2 and Ca(V)2.3 channels by mibefradil". J. Membr. Biol. 184 (2): 143–59. doi:10.1007/s00232-001-0083-4. PMID 11719851.
Pereverzev A, Leroy J, Krieger A, et al. (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". Mol. Cell. Neurosci. 21 (2): 352–65. doi:10.1006/mcne.2002.1179. PMID 12401453.
Fernandez F, Curtain RP, Colson NJ, et al. (2007). "Association analysis of chromosome 1 migraine candidate genes". BMC Med. Genet. 8: 57. doi:10.1186/1471-2350-8-57. PMC 2034370. PMID 17727731.
Vajna R, Klöckner U, Pereverzev A, et al. (2001). "Functional coupling between 'R-type' Ca2+ channels and insulin secretion in the insulinoma cell line INS-1". Eur. J. Biochem. 268 (4): 1066–75. doi:10.1046/j.1432-1327.2001.01969.x. PMID 11179973.
Muller YL, Hanson RL, Zimmerman C, et al. (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

CACNA1E protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
R-Type Calcium Channel at the US National Library of Medicine Medical 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

see also disorders

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R-type calcium channel

References

Further reading

External links