R-type calcium channel

R-type calcium channel

Calcium channel, voltage-dependent, R type, alpha 1E subunit
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; BII; CACH6; CACNL1A6; Cav2.3
External IDs IUPHAR: ChEMBL: GeneCards:
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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 Cav2.3 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.


  1. ^ "Entrez Gene: CACNA1E calcium channel, voltage-dependent, R type, alpha 1E subunit". 
  2. ^ 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.  
  3. ^ 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.  
  4. ^ 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.  

Further reading

  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • Suzuki T, Delgado-Escueta AV, Aguan K, et al. (2004). "Mutations in EFHC1 cause juvenile myoclonic epilepsy". Nat. Genet. 36 (8): 842–9.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • Fernandez F, Curtain RP, Colson NJ, et al. (2007). "Association analysis of chromosome 1 migraine candidate genes". BMC Med. Genet. 8: 57.  
  • 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.  
  • 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.  

External links