Gene Symbol: Cacna2d1
Description: calcium channel, voltage-dependent, alpha2/delta subunit 1
Alias: Ca(v)alpha2delta1, Cacna2, Cchl2a, voltage-dependent calcium channel subunit alpha-2/delta-1, dihydropyridine-sensitive calcium channel alpha 2, voltage-gated calcium channel subunit alpha-2/delta-1
Species: mouse
Products:     Cacna2d1

Top Publications

  1. Bian F, Li Z, Offord J, Davis M, McCormick J, Taylor C, et al. Calcium channel alpha2-delta type 1 subunit is the major binding protein for pregabalin in neocortex, hippocampus, amygdala, and spinal cord: an ex vivo autoradiographic study in alpha2-delta type 1 genetically modified mice. Brain Res. 2006;1075:68-80 pubmed
  2. 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. ..
  3. 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. ..
  4. Li C, Zhang X, Matthews E, Li K, Kurwa A, Boroujerdi A, et al. Calcium channel alpha2delta1 subunit mediates spinal hyperexcitability in pain modulation. Pain. 2006;125:20-34 pubmed
    ..Modulation of enhanced VGCC activity by gabapentin may underlie at least partially its antihyperalgesic actions. ..
  5. Jay S, Sharp A, Kahl S, Vedvick T, Harpold M, Campbell K. Structural characterization of the dihydropyridine-sensitive calcium channel alpha 2-subunit and the associated delta peptides. J Biol Chem. 1991;266:3287-93 pubmed
    ..The data support a model of the alpha 2-subunit in which the propeptide is processed into two chains that remain attached through disulfide linkages. ..
  6. Schlick B, Flucher B, Obermair G. Voltage-activated calcium channel expression profiles in mouse brain and cultured hippocampal neurons. Neuroscience. 2010;167:786-98 pubmed publisher
    ..Developmental changes are likely determined by an intrinsic program and not regulated by changes in neuronal activity. ..
  7. Angelotti T, Hofmann F. Tissue-specific expression of splice variants of the mouse voltage-gated calcium channel alpha2/delta subunit. FEBS Lett. 1996;397:331-7 pubmed
    ..Smooth muscle-containing tissues expressed alpha2d and alpha2e. Thus, alpha2/delta isoforms are restricted in their tissue expression, suggesting an important functional role for the differentially spliced variants. ..
  8. Chin H, Mock B, Kim H, Kim H, Kozak C. The gene for the dihydropyridine-sensitive calcium channel alpha 2 subunit (CCHL2A) maps to the proximal region of mouse chromosome 5. Genomics. 1992;13:1325-7 pubmed
    ..This gene, termed Cchl2a, was mapped near the centromeric end of the Chromosome 5 linkage group with gene order: centromere-Pgy-1-Cchl2a-Il-..
  9. Fuller Bicer G, Varadi G, Koch S, Ishii M, Bodi I, Kadeer N, et al. Targeted disruption of the voltage-dependent calcium channel alpha2/delta-1-subunit. Am J Physiol Heart Circ Physiol. 2009;297:H117-24 pubmed publisher
    ..This is a novel model for studying the function of the alpha(2)/delta-1-subunit and will be of importance in the development of new pharmacological therapies. ..

More Information


  1. Cordeira J, Felsted J, Teillon S, Daftary S, Panessiti M, Wirth J, et al. Hypothalamic dysfunction of the thrombospondin receptor ?2?-1 underlies the overeating and obesity triggered by brain-derived neurotrophic factor deficiency. J Neurosci. 2014;34:554-65 pubmed publisher
    ..They also demonstrate a novel and critical role for ?2?-1 in appetite control and suggest a mechanism underlying weight gain in humans treated with gabapentinoid drugs. ..
  2. Lau L, Noubary F, Wang D, Dulla C. α2δ-1 Signaling Drives Cell Death, Synaptogenesis, Circuit Reorganization, and Gabapentin-Mediated Neuroprotection in a Model of Insult-Induced Cortical Malformation. Eneuro. 2017;4: pubmed publisher
    ..Taken together these studies suggests that inhibiting α2δ-1 signaling may have therapeutic promise to reduce cell death and network reorganization associated with insult-induced DCMs. ..
  3. Thompson W, Majid A, Czymmek K, Ruff A, Garcia J, Duncan R, et al. Association of the ?(2)?(1) subunit with Ca(v)3.2 enhances membrane expression and regulates mechanically induced ATP release in MLO-Y4 osteocytes. J Bone Miner Res. 2011;26:2125-39 pubmed publisher
    ..2 (?(1H)) at the plasma membrane, suggesting that the diminished ATP release and ERK1/2 activation in response to membrane stretch resulted from a lack of Ca(v) 3.2 (?(1H)) at the cell membrane...
  4. Zhou C, Luo Z. Electrophysiological characterization of spinal neuron sensitization by elevated calcium channel alpha-2-delta-1 subunit protein. Eur J Pain. 2014;18:649-58 pubmed publisher
    ..Our findings support a role of peripheral nerve injury-induced ?2 ?1 in enhancing pre-synaptic excitatory input onto superficial dorsal spinal cord neurons that contributes to nociception development. ..
  5. Shibasaki M, Kurokawa K, Ohkuma S. Role of alpha2/delta subunit in the development of morphine-induced rewarding effect and behavioral sensitization. Neuroscience. 2009;163:731-4 pubmed publisher
  6. Garcia K, Nabhani T, Garcia J. The calcium channel alpha2/delta1 subunit is involved in extracellular signalling. J Physiol. 2008;586:727-38 pubmed
    ..This new role of the alpha2/delta1 subunit may be crucial for muscle development, muscle repair and at times in which myoblast attachment and migration are fundamental. ..
  7. Katsura M, Shibasaki M, Kurokawa K, Tsujimura A, Ohkuma S. Up-regulation of L-type high voltage-gated calcium channel subunits by sustained exposure to 1,4- and 1,5-benzodiazepines in cerebrocortical neurons. J Neurochem. 2007;103:2518-28 pubmed
    ..2 and Cav1.3 but also alpha2/delta1 subunit after their sustained exposure, which may participate in the development of physical dependence by these BZDs. ..
  8. Young E, Bryant C, Lee S, Peng X, Cook B, Nair H, et al. Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test. Genes Brain Behav. 2016;15:604-15 pubmed publisher
    ..candidate genes within the loci: von Frey thresholds were strongly correlated with baseline expression of Cacna2d1, Ift27 and Csnk1e in multiple brain regions of BXD strains...
  9. Joshi I, Taylor C. Pregabalin action at a model synapse: binding to presynaptic calcium channel alpha2-delta subunit reduces neurotransmission in mice. Eur J Pharmacol. 2006;553:82-8 pubmed
  10. Lyu Y, Lin C, Azarova A, Cai L, Wang J, Liu L. Role of topoisomerase IIbeta in the expression of developmentally regulated genes. Mol Cell Biol. 2006;26:7929-41 pubmed
    ..Together, these results support a role of TopIIbeta in activation/repression of developmentally regulated genes at late stages of neuronal differentiation. ..
  11. Montgomery J, Guarnieri M, Tartaglia K, Flaherty L. High-resolution genetic map and YAC contig around the mouse neurological locus reeler. Mamm Genome. 1994;5:756-61 pubmed
    ..A yeast artificial chromosome contig consisting of clones containing two of these loci, D5Mit72 (located 0.31 cM distal to rl), and D5Mit61 (no recombinants with rl), has been assembled and is being used to locate the rl gene. ..
  12. Gómez Herreros F, Schuurs Hoeijmakers J, McCormack M, Greally M, Rulten S, Romero Granados R, et al. TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function. Nat Genet. 2014;46:516-21 pubmed publisher
    ..Collectively, these data implicate chromosome breakage by TOP2 as an endogenous threat to gene transcription and to normal neuronal development and maintenance. ..
  13. Mastrolia V, Flucher S, Obermair G, Drach M, Hofer H, Renstrom E, et al. Loss of ?2?-1 Calcium Channel Subunit Function Increases the Susceptibility for Diabetes. Diabetes. 2017;66:897-907 pubmed publisher
    ..Together, these findings demonstrate that the loss of the Ca2+ channel ?2?-1 subunit function increases the susceptibility for developing diabetes in a sex-dependent manner. ..
  14. Patel R, Bauer C, Nieto Rostro M, Margas W, Ferron L, Chaggar K, et al. α2δ-1 gene deletion affects somatosensory neuron function and delays mechanical hypersensitivity in response to peripheral nerve damage. J Neurosci. 2013;33:16412-26 pubmed publisher
    ..Thus, α2δ-1 is essential for rapid development of mechanical hypersensitivity in a nerve injury model of neuropathic pain. ..
  15. Faria L, Gu F, Parada I, Barres B, Luo Z, Prince D. Epileptiform activity and behavioral arrests in mice overexpressing the calcium channel subunit α2δ-1. Neurobiol Dis. 2017;102:70-80 pubmed publisher
  16. Dolphin A. Calcium channel auxiliary ?2? and ? subunits: trafficking and one step beyond. Nat Rev Neurosci. 2012;13:542-55 pubmed publisher
    ..The aim of this Review is to examine both the classic and novel roles for these auxiliary subunits in voltage-gated calcium channel function and beyond. ..
  17. Senatore A, Colleoni S, Verderio C, Restelli E, Morini R, Condliffe S, et al. Mutant PrP suppresses glutamatergic neurotransmission in cerebellar granule neurons by impairing membrane delivery of VGCC ?(2)?-1 Subunit. Neuron. 2012;74:300-13 pubmed publisher
    ..These results link intracellular PrP retention to synaptic dysfunction, indicating new modalities of neurotoxicity and potential therapeutic strategies. ..
  18. Wada K, Zimmerman K, Adamson M, Yokotani N, Wenthold R, Kozak C. Genetic mapping of the mouse gene encoding dipeptidyl aminopeptidase-like proteins. Mamm Genome. 1993;4:234-7 pubmed
  19. Lotarski S, Donevan S, El Kattan A, Osgood S, Poe J, Taylor C, et al. Anxiolytic-like activity of pregabalin in the Vogel conflict test in ?2?-1 (R217A) and ?2?-2 (R279A) mouse mutants. J Pharmacol Exp Ther. 2011;338:615-21 pubmed publisher
    ..The positive control phenobarbital was active in mice carrying either mutation. These data suggest that the anxiolytic-like effects of pregabalin are mediated by binding of the drug to the ?(2)?-1 subunit. ..
  20. Lee C, Kozak C, Yamada K. Structure, genetic mapping, and expression of the mouse Hgf/scatter factor gene. Cell Adhes Commun. 1993;1:101-11 pubmed
    ..The relationship of Hgf to the reeler mutation is discussed. The availability of mouse HGF/SF cDNA clones should facilitate further analysis of HGF/SF function during development. ..
  21. Ohshima T, Nagle J, Pant H, Joshi J, Kozak C, Brady R, et al. Molecular cloning and chromosomal mapping of the mouse cyclin-dependent kinase 5 gene. Genomics. 1995;28:585-8 pubmed
    ..Mouse Cdk5 was mapped to the centromeric region of mouse chromosome 5. ..
  22. Garcia J. The calcium channel ?2/?1 subunit interacts with ATP5b in the plasma membrane of developing muscle cells. Am J Physiol Cell Physiol. 2011;301:C44-52 pubmed publisher
    ..Our data indicate that the ?2/?1 subunit is not only part of the DHPR but that it may interact with other cellular components in developing myotubes, such as the ATP5b in its atypical localization in the plasma membrane. ..
  23. Nguyen D, Deng P, Matthews E, Kim D, Feng G, Dickenson A, et al. Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity. Mol Pain. 2009;5:6 pubmed publisher
    ..This spinal sensitization mechanism may mediate at least partially the neuropathic pain states derived from increased pre-synaptic Cavalpha2delta1 expression. ..
  24. 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. ..
  25. Katsura M, Shibasaki M, Hayashida S, Torigoe F, Tsujimura A, Ohkuma S. Increase in expression of alpha1 and alpha2/delta1 subunits of L-type high voltage-gated calcium channels after sustained ethanol exposure in cerebral cortical neurons. J Pharmacol Sci. 2006;102:221-30 pubmed
  26. 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. ..
  27. Shibasaki M, Katsura M, Kurokawa K, Torigoe F, Ohkuma S. Regional differences of L-type high voltage-gated calcium channel subunit expression in the mouse brain after chronic morphine treatment. J Pharmacol Sci. 2007;105:177-83 pubmed
    ..These results indicate that the increased L-type HVCC subunits in the cerebral cortex and mesolimbic region participate in the development of morphine physical dependence. ..
  28. Etemad S, Obermair G, Bindreither D, Benedetti A, Stanika R, Di Biase V, et al. Differential neuronal targeting of a new and two known calcium channel ?4 subunit splice variants correlates with their regulation of gene expression. J Neurosci. 2014;34:1446-61 pubmed publisher
  29. Beckers M, Bar I, Huynh Thu T, Dernoncourt C, Brunialti A, Montagutelli X, et al. A high-resolution genetic map of mouse chromosome 5 encompassing the reeler (rl) locus. Genomics. 1994;23:685-90 pubmed
    ..The following order was defined: (centromere)-Cchl2a/Hgf-D5Mit1-D5Nam1/D5-Nam2 -rl/D5Mit61-D5Mit72-Xmv45-Htr5a- Peplb-D5Nam3-D5Mit66...
  30. de Sevilla Müller L, Liu J, Solomon A, Rodriguez A, Brecha N. Expression of voltage-gated calcium channel ?(2)?(4) subunits in the mouse and rat retina. J Comp Neurol. 2013;521:2486-501 pubmed publisher
  31. Nasca C, Orlando R, Marchiafava M, Boldrini P, Battaglia G, Scaccianoce S, et al. Exposure to predator odor and resulting anxiety enhances the expression of the ?2 ? subunit of voltage-sensitive calcium channels in the amygdala. J Neurochem. 2013;125:649-56 pubmed publisher
    ..These data offer the first demonstration that the ?2 ?-1 subunit of VSCCs undergoes plastic changes in a model of innate anxiety, and supports the use of pregabalin as a disease-dependent drug in the treatment of anxiety disorders. ..
  32. Bauer C, Tran Van Minh A, Kadurin I, Dolphin A. A new look at calcium channel ?2? subunits. Curr Opin Neurobiol. 2010;20:563-71 pubmed publisher
    ..Furthermore, gabapentinoid drugs, which bind to ?(2)?-1 and ?(2)?-2, not only impair their trafficking, but also affect ?(2)?-1-dependent synaptogenesis. These drugs may interfere with ?(2)? function at several different levels. ..
  33. Tsukumo Y, Matsumoto Y, Miura H, Yano H, Manabe H. Gabapentin and pregabalin inhibit the itch-associated response induced by the repeated application of oxazolone in mice. J Pharmacol Sci. 2011;115:27-35 pubmed
    ..These results suggest that gabapentin and pregabalin show an anti-pruritic activity through ???-subunit binding, and the up-regulation of the ???-1 subunit in DRG may therefore play an important role in its anti-pruritic activity. ..
  34. Park J, Yu Y, Zhou C, Li K, Wang D, Chang E, et al. Central Mechanisms Mediating Thrombospondin-4-induced Pain States. J Biol Chem. 2016;291:13335-48 pubmed publisher
  35. Field M, Cox P, Stott E, Melrose H, Offord J, Su T, et al. Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci U S A. 2006;103:17537-42 pubmed
    ..These studies show conclusively that the analgesic actions of pregabalin are mediated through the alpha2-delta-1 subunit of voltage-gated calcium channels and establish this subunit as a therapeutic target for pain control. ..
  36. Templin J, Bang S, Soiza Reilly M, Berde C, Commons K. Patterned expression of ion channel genes in mouse dorsal raphe nucleus determined with the Allen Mouse Brain Atlas. Brain Res. 2012;1457:1-12 pubmed publisher
    ..The identified genes likely contribute to unique excitable properties of different groups of neurons in the DR and may include novel pharmacologic targets for affective disorders. ..
  37. Kurokawa K, Shibasaki M, Mizuno K, Ohkuma S. Gabapentin blocks methamphetamine-induced sensitization and conditioned place preference via inhibition of ??/?-1 subunits of the voltage-gated calcium channels. Neuroscience. 2011;176:328-35 pubmed publisher