Gene Symbol: Cacna2d1
Description: calcium voltage-gated channel auxiliary subunit alpha2delta 1
Alias: CCHLA2, Cacna2, DHSCCA, voltage-dependent calcium channel subunit alpha-2/delta-1, Calcium channel subunit alpha 2 delta (dihydropyridine - sensitive L-type), calcium channel, voltage-dependent, alpha2/delta subunit 1, voltage-gated calcium channel subunit alpha-2/delta-1
Species: rat
Products:     Cacna2d1

Top Publications

  1. Li C, Song Y, Higuera E, Luo Z. Spinal dorsal horn calcium channel alpha2delta-1 subunit upregulation contributes to peripheral nerve injury-induced tactile allodynia. J Neurosci. 2004;24:8494-9 pubmed
    ..Thus, changes in presynaptic alpha2delta-1 subunit expression contribute to injury-induced spinal neuroplasticity and central sensitization that underlies neuropathic pain development and maintenance. ..
  2. Worst T, Tan J, Robertson D, Freeman W, Hyytia P, Kiianmaa K, et al. Transcriptome analysis of frontal cortex in alcohol-preferring and nonpreferring rats. J Neurosci Res. 2005;80:529-38 pubmed
    ..ANA lines. In contrast, calcium channel subunit alpha2delta1 (cacna2d1), vesicle-associated membrane protein 2 (VAMP2), syntaxin 1 (both syntaxin 1a and 1b; STX1a and STX1b), and ..
  3. Lana B, Schlick B, Martin S, Pratt W, Page K, Gonçalves L, et al. Differential upregulation in DRG neurons of an ?2?-1 splice variant with a lower affinity for gabapentin after peripheral sensory nerve injury. Pain. 2014;155:522-33 pubmed publisher
    ..This variant could therefore play a role in determining the efficacy of gabapentin in neuropathic pain. ..
  4. Taylor C, Garrido R. Immunostaining of rat brain, spinal cord, sensory neurons and skeletal muscle for calcium channel alpha2-delta (alpha2-delta) type 1 protein. Neuroscience. 2008;155:510-21 pubmed publisher
    ..We propose that areas of dense alpha2-delta-1 staining in brain and spinal cord are likely sites of action for the analgesic, anticonvulsant and anxiolytic-like actions of pregabalin and gabapentin in animal models. ..
  5. Antzelevitch C, Pollevick G, Cordeiro J, Casis O, Sanguinetti M, Aizawa Y, et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation. 2007;115:442-9 pubmed
    ..performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b (Ca(v beta2b)), CACNA2D1 (Ca(v alpha2delta1)), and CACNA1C tagged with enhanced yellow fluorescent protein (Ca(v)1.2)...
  6. Davies A, Kadurin I, Alvarez Laviada A, Douglas L, Nieto Rostro M, Bauer C, et al. The alpha2delta subunits of voltage-gated calcium channels form GPI-anchored proteins, a posttranslational modification essential for function. Proc Natl Acad Sci U S A. 2010;107:1654-9 pubmed publisher
    ..In conclusion, this study redefines our understanding of alpha(2)delta subunits, both in terms of their role in calcium-channel function and other roles in synaptogenesis. ..
  7. Eroglu C, Allen N, Susman M, O Rourke N, Park C, Ozkan E, et al. Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell. 2009;139:380-92 pubmed publisher
    ..These findings identify alpha2delta-1 as a receptor involved in excitatory synapse formation and suggest that gabapentin may function therapeutically by blocking new synapse formation. ..
  8. Robinson P, Etheridge S, Song L, Armenise P, Jones O, Fitzgerald E. Formation of N-type (Cav2.2) voltage-gated calcium channel membrane microdomains: Lipid raft association and clustering. Cell Calcium. 2010;48:183-94 pubmed publisher
    ..However, formation of clusters supporting "hotspots" of Ca(v) activity requires aggregation of macromolecular complexes containing raft components, stabilised by interactions with the cytoskeleton. ..
  9. Cole R, Lechner S, Williams M, Prodanovich P, Bleicher L, Varney M, et al. Differential distribution of voltage-gated calcium channel alpha-2 delta (alpha2delta) subunit mRNA-containing cells in the rat central nervous system and the dorsal root ganglia. J Comp Neurol. 2005;491:246-69 pubmed
    ..In addition to being localized in brain regions that express alpha2delta-1 and alpha2delta-2 subunit mRNAs, alpha2delta-3 subunit mRNA is highly expressed in regions involved in auditory information processing and somatic movement. ..

More Information


  1. Cens T, Rousset M, Charnet P. Two sets of amino acids of the domain I of Cav2.3 Ca(2+) channels contribute to their high sensitivity to extracellular protons. Pflugers Arch. 2011;462:303-14 pubmed publisher
  2. Templin C, Ghadri J, Rougier J, Baumer A, Kaplan V, Albesa M, et al. Identification of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6). Eur Heart J. 2011;32:1077-88 pubmed publisher mutation in previously known SQTS genes; however, a new variant at a heterozygous state was identified in the CACNA2D1 gene (nucleotide c.2264G > C; amino acid p...
  3. Quintero J, Dooley D, Pomerleau F, Huettl P, Gerhardt G. Amperometric measurement of glutamate release modulation by gabapentin and pregabalin in rat neocortical slices: role of voltage-sensitive Ca2+ ?2?-1 subunit. J Pharmacol Exp Ther. 2011;338:240-5 pubmed publisher
    ..The results show that GBP and PGB attenuated stimulus-evoked glutamate release in rodent neocortical slices and that the ?(2)?-1 subunit of VSCC appears to mediate this effect. ..
  4. Mezler M, Barghorn S, Schoemaker H, Gross G, Nimmrich V. A ?-amyloid oligomer directly modulates P/Q-type calcium currents in Xenopus oocytes. Br J Pharmacol. 2012;165:1572-83 pubmed publisher
    ..Threshold reduction as well as an increase in current at synaptic terminals may facilitate vesicle release and could trigger excitotoxic events in the brains of patients with AD. ..
  5. Farrell S, Sargoy A, Brecha N, Barnes S. Modulation of voltage-gated Ca2+ channels in rat retinal ganglion cells by gabapentin. Vis Neurosci. 2014;31:47-55 pubmed publisher
    ..Some Ca2+ channel blockers have been shown to protect RGCs in retinal trauma suggesting that modulation of VGCCs by gabapentin may prevent the deleterious effects of elevated Ca2+ levels in RGCs in trauma and disease. ..
  6. Grimaldo L, Sandoval A, Garza López E, Felix R. Involvement of Parkin in the ubiquitin proteasome system-mediated degradation of N-type voltage-gated Ca2+ channels. PLoS ONE. 2017;12:e0185289 pubmed publisher
    ..Together these results unveil a novel functional coupling between Parkin and the CaV2.2 channels and provide a novel insight into the basic mechanisms of CaV channels protein quality control and functional expression. ..
  7. Favereaux A, Thoumine O, Bouali Benazzouz R, Roques V, Papon M, Salam S, et al. Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain. EMBO J. 2011;30:3830-41 pubmed publisher
    ..Moreover, we demonstrate that miR-103 is down-regulated in neuropathic animals and that miR-103 intrathecal applications successfully relieve pain, identifying miR-103 as a novel possible therapeutic target in neuropathic chronic pain. ..
  8. Cassidy J, Ferron L, Kadurin I, Pratt W, Dolphin A. Functional exofacially tagged N-type calcium channels elucidate the interaction with auxiliary α2δ-1 subunits. Proc Natl Acad Sci U S A. 2014;111:8979-84 pubmed publisher
    ..2 and α2δ-1 is not disrupted by gabapentin. Altogether, these results demonstrate that CaV2.2 and α2δ-1 are intimately associated at the plasma membrane and allow us to infer a region of interaction. ..
  9. Wang Y, Zhang M, Xie F, Li X, Bao M, Yang N, et al. Upregulation of α₂δ-1 Calcium Channel Subunit in the Spinal Cord Contributes to Pelvic Organ Cross-Sensitization in a Rat Model of Experimentally-Induced Endometriosis. Neurochem Res. 2015;40:1267-73 pubmed publisher
    ..Our study may provide a biological basis for selectively targeting this pathway to relieve viscero-visceral referred hyperalgesia in patients with painful endometriosis. ..
  10. Obermair G, Kugler G, Baumgartner S, Tuluc P, Grabner M, Flucher B. The Ca2+ channel alpha2delta-1 subunit determines Ca2+ current kinetics in skeletal muscle but not targeting of alpha1S or excitation-contraction coupling. J Biol Chem. 2005;280:2229-37 pubmed
    ..However, this subunit is not essential for targeting of Ca(2+) channels or for their primary physiological role in activating skeletal muscle excitation-contraction coupling. ..
  11. Yamada Y, Nagashima M, Tsutsuura M, Kobayashi T, Seki S, Makita N, et al. Cloning of a functional splice variant of L-type calcium channel beta 2 subunit from rat heart. J Biol Chem. 2001;276:47163-70 pubmed
    ..Taken together, these observations suggest that the beta(2c) subunit is a functional beta(2) subunit expressed in heart and that the short N-terminal region plays a major role in modifying inactivation kinetics. ..
  12. Chu P, Best P. Molecular cloning of calcium channel alpha(2)delta-subunits from rat atria and the differential regulation of their expression by IGF-1. J Mol Cell Cardiol. 2003;35:207-15 pubmed
    ..Differential regulation of the expression of alpha(2)delta-subunit genes is likely to contribute to alterations in the expression of calcium current in the mammalian heart. ..
  13. Kadurin I, Ferron L, Rothwell S, Meyer J, Douglas L, Bauer C, et al. Proteolytic maturation of ?2? represents a checkpoint for activation and neuronal trafficking of latent calcium channels. elife. 2016;5: pubmed publisher
    ..Proteolytic processing of ?2? then permits voltage-dependent activation of the channels, acting as a checkpoint allowing trafficking only of mature calcium channel complexes into neuronal processes. ..
  14. Boroujerdi A, Zeng J, Sharp K, Kim D, Steward O, Luo Z. Calcium channel alpha-2-delta-1 protein upregulation in dorsal spinal cord mediates spinal cord injury-induced neuropathic pain states. Pain. 2011;152:649-55 pubmed publisher
    ..Spinal cord contusion injury caused increased calcium channel Ca(v)?2?-1 subunit expression in dorsal spinal cord that contributes to neuropathic pain states. ..
  15. Spencer S, Brown R, Quintero G, Kupchik Y, Thomas C, Reissner K, et al. ?2?-1 signaling in nucleus accumbens is necessary for cocaine-induced relapse. J Neurosci. 2014;34:8605-11 pubmed publisher
    ..These results also inform ongoing discussion in the literature regarding efficacy of gabapentin as a candidate addiction therapy. ..
  16. Bell D, Butcher A, Berrow N, Page K, Brust P, Nesterova A, et al. Biophysical properties, pharmacology, and modulation of human, neuronal L-type (alpha(1D), Ca(V)1.3) voltage-dependent calcium currents. J Neurophysiol. 2001;85:816-27 pubmed
  17. Lin Y, McDonough S, Lipscombe D. Alternative splicing in the voltage-sensing region of N-Type CaV2.2 channels modulates channel kinetics. J Neurophysiol. 2004;92:2820-30 pubmed
    ..Our results suggest that alternative splicing in the S3-S4 linker influences the kinetics but not the voltage dependence of N-type channel gating. ..
  18. Calderón Rivera A, Andrade A, Hernandez Hernandez O, González Ramírez R, Sandoval A, Rivera M, et al. Identification of a disulfide bridge essential for structure and function of the voltage-gated Ca(2+) channel ?(2)?-1 auxiliary subunit. Cell Calcium. 2012;51:22-30 pubmed publisher
    ..2?(1)/?(3)) channels, showed decreased whole-cell patch-clamp currents indicating that the disulfide bond between these residues is required for ?(2)?-1 function. ..
  19. Simms B, Souza I, Zamponi G. Effect of the Brugada syndrome mutation A39V on calmodulin regulation of Cav1.2 channels. Mol Brain. 2014;7:34 pubmed publisher
    ..Our data indicate that caution must be exercised when interpreting the effects of CaM mutants on ion channel gating. ..
  20. Williams M, Feldman D, McCue A, Brenner R, Velicelebi G, Ellis S, et al. Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype. Neuron. 1992;8:71-84 pubmed
    ..At least two forms of neuronal alpha 1D were identified. Different forms of alpha 2 and beta transcripts were also identified in CNS, skeletal muscle, and aorta tissues. ..
  21. Song L, Espinoza Fuenzalida I, Etheridge S, Jones O, Fitzgerald E. The R-Domain: Identification of an N-terminal Region of the α2δ-1 Subunit Which is Necessary and Sufficient for its Effects on Cav2.2 Calcium Currents. Curr Mol Pharmacol. 2015;8:169-79 pubmed
    ..We suggest, therefore, that Rd likely constitutes the major locus for physical interaction with the α1 subunit and may provide a target for novel Cav therapeutics. ..
  22. Bannister J, Bulley S, Narayanan D, Thomas Gatewood C, Luzny P, Pachuau J, et al. Transcriptional upregulation of ?2?-1 elevates arterial smooth muscle cell voltage-dependent Ca2+ channel surface expression and cerebrovascular constriction in genetic hypertension. Hypertension. 2012;60:1006-15 pubmed publisher
    ..Data also suggest that ?2?-1 targeting is a novel strategy that may be used to reverse pathological CaV1.2 channel trafficking to induce cerebrovascular dilation in hypertension. ..
  23. Cens T, Rousset M, Kajava A, Charnet P. Molecular determinant for specific Ca/Ba selectivity profiles of low and high threshold Ca2+ channels. J Gen Physiol. 2007;130:415-25 pubmed
    ..These data therefore attribute to the DCS a unique role in the specific shaping of the Ca(2+) influx between the different HVA channels...
  24. Nieto Rostro M, Sandhu G, Bauer C, Jiruska P, Jefferys J, Dolphin A. Altered expression of the voltage-gated calcium channel subunit α₂δ-1: a comparison between two experimental models of epilepsy and a sensory nerve ligation model of neuropathic pain. Neuroscience. 2014;283:124-37 pubmed publisher
  25. Robinson P, Etheridge S, Song L, Shah R, Fitzgerald E, Jones O. Targeting of voltage-gated calcium channel ?2?-1 subunit to lipid rafts is independent from a GPI-anchoring motif. PLoS ONE. 2011;6:e19802 pubmed publisher
  26. Bourdin B, Marger F, Wall Lacelle S, Schneider T, Klein H, Sauve R, et al. Molecular determinants of the CaVbeta-induced plasma membrane targeting of the CaV1.2 channel. J Biol Chem. 2010;285:22853-63 pubmed publisher
    ..2. Altogether, these data support a model where high affinity binding of Ca(V)beta to the I-II linker of Ca(V)alpha1 largely accounts for Ca(V)beta-induced plasma membrane targeting of Ca(V)1.2. ..
  27. Huang J, Zhou L, Wang H, Luo J, Zeng L, Xiong K, et al. Distribution of thrombospondins and their neuronal receptor ?2?1 in the rat retina. Exp Eye Res. 2013;111:36-49 pubmed publisher
    ..Our study suggested that in the adult rat retina, TSP2, but not TSP1, secreted by glial cells may be involved in the synaptic plastic process after retinal injury through binding to its neuronal receptor ?2?1...
  28. Bourdin B, Shakeri B, Tétreault M, Sauvé R, Lesage S, Parent L. Functional characterization of CaVα2δ mutations associated with sudden cardiac death. J Biol Chem. 2015;290:2854-69 pubmed publisher
    ..The functional impact of genetic variants of CACNA2D1 (the gene encoding for CaVα2δ), associated with shorter repolarization QT intervals (the time interval ..
  29. Andrade A, Sandoval A, González Ramírez R, Lipscombe D, Campbell K, Felix R. The alpha(2)delta subunit augments functional expression and modifies the pharmacology of Ca(V)1.3 L-type channels. Cell Calcium. 2009;46:282-92 pubmed publisher
    ..3 channels possibly by affecting channel synthesis. Together these results provide several lines of evidence that the Ca(V)alpha(2)delta-1 auxiliary subunit may interact with Ca(V)1.3 channels and regulate their functional expression. ..
  30. Kim H, Kim H, Lee P, King R, Chin H. Rat brain expresses an alternatively spliced form of the dihydropyridine-sensitive L-type calcium channel alpha 2 subunit. Proc Natl Acad Sci U S A. 1992;89:3251-5 pubmed
  31. Tétreault M, Bourdin B, Briot J, Segura E, Lesage S, Fiset C, et al. Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity. J Biol Chem. 2016;291:4826-43 pubmed publisher
  32. Lencesova L, O Neill A, Resneck W, Bloch R, Blaustein M. Plasma membrane-cytoskeleton-endoplasmic reticulum complexes in neurons and astrocytes. J Biol Chem. 2004;279:2885-93 pubmed
    ..These PM and ER components appear to be linked through the cytoskeletal spectrin network, to which they are probably tethered by Ank 2. ..