Gene Symbol: Cacna1e
Description: calcium channel, voltage-dependent, R type, alpha 1E subunit
Alias: A430040I15, BII, Cach6, Cacnl1a6, Cav2.3, Cchra1, alpha1E, voltage-dependent R-type calcium channel subunit alpha-1E, brain calcium channel II, calcium channel, L type, alpha-1 polypeptide, calcium channel, voltage-dependent, L type, alpha 1E subunit, voltage-gated calcium channel subunit alpha Cav2.3
Species: mouse
Products:     Cacna1e

Top Publications

  1. Bloodgood B, Sabatini B. Nonlinear regulation of unitary synaptic signals by CaV(2.3) voltage-sensitive calcium channels located in dendritic spines. Neuron. 2007;53:249-60 pubmed
    ..Our results suggest that synaptic strength can be modulated by mechanisms that regulate voltage-gated conductances within the spine but do not alter the properties or numbers of synaptic glutamate receptors. ..
  2. Wilson S, Toth P, Oh S, Gillard S, Volsen S, Ren D, et al. The status of voltage-dependent calcium channels in alpha 1E knock-out mice. J Neurosci. 2000;20:8566-71 pubmed
    ..We conclude that there exists a component of the R current that results from the expression of the alpha(1E) Ca channel subunit but that the majority of R currents must result from the expression of other Ca channel alpha subunits. ..
  3. Pereverzev A, Mikhna M, Vajna R, Gissel C, Henry M, Weiergräber M, et al. Disturbances in glucose-tolerance, insulin-release, and stress-induced hyperglycemia upon disruption of the Ca(v)2.3 (alpha 1E) subunit of voltage-gated Ca(2+) channels. Mol Endocrinol. 2002;16:884-95 pubmed
    ..3-deficient mice has dual components related to endocrine and neurological defects. The present findings provide direct evidence of a functional role for the Ca(v)2.3 subunit in hormone secretion and glucose homeostasis. ..
  4. Missler M, Zhang W, Rohlmann A, Kattenstroth G, Hammer R, Gottmann K, et al. Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis. Nature. 2003;423:939-48 pubmed
    ..These data suggest that alpha-neurexins organize presynaptic terminals by functionally coupling Ca2+ channels to the presynaptic machinery. ..
  5. Xu M, Welling A, Paparisto S, Hofmann F, Klugbauer N. Enhanced expression of L-type Cav1.3 calcium channels in murine embryonic hearts from Cav1.2-deficient mice. J Biol Chem. 2003;278:40837-41 pubmed
    ..2 (-/-) cardiomyocytes. In summary, our results imply that calcium channel expression is dynamically regulated during heart development and that the Cav1.3 channel may substitute for Cav1.2 during early embryogenesis. ..
  6. Weiergräber M, Henry M, Radhakrishnan K, Hescheler J, Schneider T. Hippocampal seizure resistance and reduced neuronal excitotoxicity in mice lacking the Cav2.3 E/R-type voltage-gated calcium channel. J Neurophysiol. 2007;97:3660-9 pubmed
    ..3 voltage-gated calcium channel plays a crucial role in both hippocampal ictogenesis and seizure generalization and is of central importance in neuronal degeneration after excitotoxic events. ..
  7. Sochivko D, Pereverzev A, Smyth N, Gissel C, Schneider T, Beck H. The Ca(V)2.3 Ca(2+) channel subunit contributes to R-type Ca(2+) currents in murine hippocampal and neocortical neurones. J Physiol. 2002;542:699-710 pubmed
    ..3 subunits underlie a significant fraction of I(Ca,R) in different types of central neurones. They also indicate that Ca(V)2.3 subunits may give rise to Ca(2+) currents with differing pharmacological properties in native neurones. ..
  8. 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. ..
  9. Takei T, Saegusa H, Zong S, Murakoshi T, Makita K, Tanabe T. Anesthetic sensitivities to propofol and halothane in mice lacking the R-type (Cav2.3) Ca2+ channel. Anesth Analg. 2003;97:96-103, table of contents pubmed
    ..3) Ca(2+) channels both in vivo and in hippocampal slices. Decreased sensitivities in mutant mice imply a possibility that agents blocking this channel may increase the requirements of anesthetics/hypnotics. ..

More Information


  1. Sakata Y, Saegusa H, Zong S, Osanai M, Murakoshi T, Shimizu Y, et al. Ca(v)2.3 (alpha1E) Ca2+ channel participates in the control of sperm function. FEBS Lett. 2002;516:229-33 pubmed
    To know the function of the Ca2+ channel containing alpha(1)2.3 (alpha1E) subunit (Ca(v)2.3 channel) in spermatozoa, we analyzed Ca2+ transients and sperm motility using a mouse strain lacking Ca(v)2.3 channel...
  2. Hill J, Chan S, Kuri B, Smith C. Pituitary adenylate cyclase-activating peptide (PACAP) recruits low voltage-activated T-type calcium influx under acute sympathetic stimulation in mouse adrenal chromaffin cells. J Biol Chem. 2011;286:42459-69 pubmed publisher
    ..2 Ca(2+) influx. This in turn evokes catecholamine release during the acute sympathetic stress response. ..
  3. Ino M, Yoshinaga T, Wakamori M, Miyamoto N, Takahashi E, Sonoda J, et al. Functional disorders of the sympathetic nervous system in mice lacking the alpha 1B subunit (Cav 2.2) of N-type calcium channels. Proc Natl Acad Sci U S A. 2001;98:5323-8 pubmed
  4. Kaja S, van de Ven R, Ferrari M, Frants R, van den Maagdenberg A, Plomp J. Compensatory contribution of Cav2.3 channels to acetylcholine release at the neuromuscular junction of tottering mice. J Neurophysiol. 2006;95:2698-704 pubmed
    ..This is the first report of compensatory expression of non-Cav2.1 channels at NMJs of mice with a single amino acid change in Cav2.1. ..
  5. Park J, Remy S, VARELA J, Cooper D, Chung S, Kang H, et al. A post-burst after depolarization is mediated by group i metabotropic glutamate receptor-dependent upregulation of Ca(v)2.3 R-type calcium channels in CA1 pyramidal neurons. PLoS Biol. 2010;8:e1000534 pubmed publisher
    ..3 R-type channels that are activated during spiking at physiologically relevant rates and patterns. ..
  6. Murakami M, Nakagawasai O, Suzuki T, Mobarakeh I, Sakurada Y, Murata A, et al. Antinociceptive effect of different types of calcium channel inhibitors and the distribution of various calcium channel alpha 1 subunits in the dorsal horn of spinal cord in mice. Brain Res. 2004;1024:122-9 pubmed
    ..The results of this study revealed the localization and functions of several calcium channels that are involved in nociceptive neurotransmission within the dorsal horn of the mouse spinal cord. ..
  7. Yokoyama K, Kurihara T, Saegusa H, Zong S, Makita K, Tanabe T. Blocking the R-type (Cav2.3) Ca2+ channel enhanced morphine analgesia and reduced morphine tolerance. Eur J Neurosci. 2004;20:3516-9 pubmed
    ..3(-/-) mice. Furthermore, i.c.v. administration of an R-type channel blocker potentiated morphine analgesia in wild-type mice. Thus, the inhibition of R-type Ca(2+) current could lead to high-efficiency opioid therapy without tolerance. ..
  8. Osanai M, Saegusa H, Kazuno A, Nagayama S, Hu Q, Zong S, et al. Altered cerebellar function in mice lacking CaV2.3 Ca2+ channel. Biochem Biophys Res Commun. 2006;344:920-5 pubmed
    ..3 mutant mice in a gene dosage-dependent manner, suggesting that Ca(V)2.3 channel contributed to spike generation in Purkinje cells. Thus, Ca(V)2.3 channel seems to play some roles in cerebellar functions. ..
  9. Alnawaiseh M, Albanna W, Chen C, Campbell K, Hescheler J, Lüke M, et al. Two separate Ni(2+) -sensitive voltage-gated Ca(2+) channels modulate transretinal signalling in the isolated murine retina. Acta Ophthalmol. 2011;89:e579-90 pubmed publisher
  10. Toriyama H, Wang L, Saegusa H, Zong S, Osanai M, Murakoshi T, et al. Role of Ca(v) 2.3 (alpha1E ) Ca2+ channel in ischemic neuronal injury. Neuroreport. 2002;13:261-5 pubmed
    We investigated the role of the Ca(v)2.3 (alpha1E) channel in ischemic neuronal injury using Ca(v)2.3 mutant mice...
  11. Muller R, Struck H, Ho M, Brockhaus Dumke A, Klosterkotter J, Broich K, et al. Atropine-sensitive hippocampal ? oscillations are mediated by Cav2.3 R-type Ca²? channels. Neuroscience. 2012;205:125-39 pubmed publisher
    ..3 Ca²? channels. Our data suggest, for the first time, that Ca(v)2.3 voltage-gated Ca²? channels (VGCC) are an important factor in septohippocampal synchronization associated with theta oscillation. ..
  12. Galetin T, Tevoufouet E, Sandmeyer J, Matthes J, Nguemo F, Hescheler J, et al. Pharmacoresistant Cav 2·3 (E-type/R-type) voltage-gated calcium channels influence heart rate dynamics and may contribute to cardiac impulse conduction. Cell Biochem Funct. 2013;31:434-49 pubmed publisher
    ..Thus, Cav 2·3 does not only contribute to the cardiac autonomous nervous system but also to intrinsic rhythm propagation. ..
  13. Siwek M, Muller R, Henseler C, Broich K, Papazoglou A, Weiergräber M. The CaV2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture. Sleep. 2014;37:881-92 pubmed publisher
  14. Yamazaki K, Oki T, Tanaka I. Cloning of 5'-flanking region and a polymorphic CTT trinucleotide repeat within 5'-untranslated region of mouse R-type calcium channel alpha1-subunit (Cchra1) gene, and its genetic mapping. Gene. 1998;214:199-204 pubmed
    The 5'-flanking region of the mouse R-type calcium channel (Cchra1) gene was cloned, and a transcriptional start point (tsp) was determined by rapid amplification of 5'-cDNA end (5'RACE) method...
  15. Lyu M, Kozak C, Chin H. Genetic mapping of the gene encoding the alpha1 subunit of neuronal calcium channels. Mamm Genome. 1996;7:326-7 pubmed
  16. Gandla J, Lomada S, Lu J, Kuner R, Bali K. miR-34c-5p functions as pronociceptive microRNA in cancer pain by targeting Cav2.3 containing calcium channels. Pain. 2017;158:1765-1779 pubmed publisher
    ..The current study facilitates a deeper understanding of molecular mechanisms underlying cancer pain and suggests a potential for novel therapeutic strategies targeting miR-34c-5p and Cav2.3 in cancer pain. ..
  17. Yang L, Stephens G. Effects of neuropathy on high-voltage-activated Ca(2+) current in sensory neurones. Cell Calcium. 2009;46:248-56 pubmed publisher
    ..In Ca(V)2.3(-/-) mice, PSNL-induced changes in Ca(V)1 and Ca(V)2.2 Ca(2+) current, consistent with alternative adaptive mechanisms occurring in the absence of Ca(V)2.3 subunits. ..
  18. Hildebrand M, Isope P, Miyazaki T, Nakaya T, Garcia E, Feltz A, et al. Functional coupling between mGluR1 and Cav3.1 T-type calcium channels contributes to parallel fiber-induced fast calcium signaling within Purkinje cell dendritic spines. J Neurosci. 2009;29:9668-82 pubmed publisher
    ..Our data identify a new fast calcium signaling pathway in Purkinje cell dendritic spines triggered by short burst of parallel fiber inputs and mediated by T-type calcium channels and mGluR1s. ..
  19. Zhang Q, Bengtsson M, Partridge C, Salehi A, Braun M, Cox R, et al. R-type Ca(2+)-channel-evoked CICR regulates glucose-induced somatostatin secretion. Nat Cell Biol. 2007;9:453-60 pubmed
    ..Glucose-induced somatostatin secretion is instead primarily dependent on Ca(2+)-induced Ca(2+)-release (CICR). This constitutes a novel mechanism for K(ATP)-channel-independent metabolic control of pancreatic hormone secretion. ..
  20. Drobinskaya I, Neumaier F, Pereverzev A, Hescheler J, Schneider T. Diethyldithiocarbamate-mediated zinc ion chelation reveals role of Cav2.3 channels in glucagon secretion. Biochim Biophys Acta. 2015;1853:953-64 pubmed publisher
    ..Especially under conditions of Zn2+ deficiency, ablation or dysfunction of Cav2.3 channels may lead to severe disturbances in glucose homeostasis. ..
  21. Williams M, Marubio L, Deal C, Hans M, Brust P, Philipson L, et al. Structure and functional characterization of neuronal alpha 1E calcium channel subtypes. J Biol Chem. 1994;269:22347-57 pubmed
    ..Thus, alpha 1E-mediated Ca2+ channels appear to be a pharmacologically distinct class of voltage-activated Ca2+ channels. ..
  22. Tailor C, Nouri A, Lee C, Kozak C, Kabat D. Cloning and characterization of a cell surface receptor for xenotropic and polytropic murine leukemia viruses. Proc Natl Acad Sci U S A. 1999;96:927-32 pubmed
    ..We propose that X-MLVs and P-MLVs comprise a single family of retroviruses that have coevolved in response to diversification in X-receptor genes of the host. ..
  23. Matsuda Y, Saegusa H, Zong S, Noda T, Tanabe T. Mice lacking Ca(v)2.3 (alpha1E) calcium channel exhibit hyperglycemia. Biochem Biophys Res Commun. 2001;289:791-5 pubmed
    ..These results suggest that Ca(v)2.3 channel plays a role in glucose homeostasis by reducing insulin sensitivity and that Ca(v)2.3-/- mice exhibit symptoms resembling non-insulin-dependent diabetes mellitus. ..
  24. Dietrich D, Kirschstein T, Kukley M, Pereverzev A, von der Brelie C, Schneider T, et al. Functional specialization of presynaptic Cav2.3 Ca2+ channels. Neuron. 2003;39:483-96 pubmed
  25. Giessel A, Sabatini B. Boosting of synaptic potentials and spine Ca transients by the peptide toxin SNX-482 requires alpha-1E-encoded voltage-gated Ca channels. PLoS ONE. 2011;6:e20939 pubmed publisher
    ..We find that in these mice, application of SNX-482 has no effect on glutamate-uncaging evoked synaptic potentials and Ca influx, indicating that that SNX-482 indeed acts via the Alpha-1E-encoded Ca(V)2.3 channel. ..
  26. Saegusa H, Kurihara T, Zong S, Minowa O, Kazuno A, Han W, et al. Altered pain responses in mice lacking alpha 1E subunit of the voltage-dependent Ca2+ channel. Proc Natl Acad Sci U S A. 2000;97:6132-7 pubmed
    ..These results suggest that the alpha(1E) Ca(2 +) channel controls pain behaviors by both spinal and supraspinal mechanisms. ..
  27. Sakata Y, Saegusa H, Zong S, Osanai M, Murakoshi T, Shimizu Y, et al. Analysis of Ca(2+) currents in spermatocytes from mice lacking Ca(v)2.3 (alpha(1E)) Ca(2+) channel. Biochem Biophys Res Commun. 2001;288:1032-6 pubmed
    ..3 channel makes no detectable contribution to the LVA Ca(2+) current in the pachytene spermatocyte. Instead, Ca(v)3 family such as Ca(v)3.1 may be the likely candidates responsible for the LVA currents in pachytene spermatocytes. ..
  28. Pereverzev A, Salehi A, Mikhna M, Renstrom E, Hescheler J, Weiergräber M, et al. The ablation of the Ca(v)2.3/E-type voltage-gated Ca2+ channel causes a mild phenotype despite an altered glucose induced glucagon response in isolated islets of Langerhans. Eur J Pharmacol. 2005;511:65-72 pubmed
    ..This was most obvious at the level of isolated islets suggesting that Ca(v)2.3 containing R-type voltage-gated Ca2+ channels are involved in the glucose-mediated signalling to glucagon release in mice. ..
  29. Zaman T, Lee K, Park C, Paydar A, Choi J, Cheong E, et al. Cav2.3 channels are critical for oscillatory burst discharges in the reticular thalamus and absence epilepsy. Neuron. 2011;70:95-108 pubmed publisher
    ..3 channels in the RT mimicked the results of Ca(v)2.3?/? mice. These results provide strong evidence that Ca(v)2.3 channels are critical for oscillatory burst discharges in RT neurons and for the expression of absence epilepsy. ..
  30. Han W, Saegusa H, Zong S, Tanabe T. Altered cocaine effects in mice lacking Ca(v)2.3 (alpha(1E)) calcium channel. Biochem Biophys Res Commun. 2002;299:299-304 pubmed
    ..3 channel contributes to the locomotor-stimulating effect of cocaine, and the deletion of Ca(v)2.3 channel reveals the presence of a novel pathway leading to cocaine rewarding which is insensitive to D1 receptor antagonist. ..
  31. Joksovic P, Weiergräber M, Lee W, Struck H, Schneider T, Todorovic S. Isoflurane-sensitive presynaptic R-type calcium channels contribute to inhibitory synaptic transmission in the rat thalamus. J Neurosci. 2009;29:1434-45 pubmed publisher
    ..In addition, isoflurane potently blocked currents in recombinant human Ca(V)2.3 (alpha1E) channels with an IC(50) of 206 +/- 22 mum...
  32. Jones L, McCarthy K, Beard J, Keen C, Jones B. Quantitative genetic analysis of brain copper and zinc in BXD recombinant inbred mice. Nutr Neurosci. 2006;9:81-92 pubmed
    ..More importantly, revelation of the genetic underpinnings of copper and zinc brain homeostasis will aid our understanding of neurological diseases that are related to copper and zinc imbalance. ..
  33. Jing X, Li D, Olofsson C, Salehi A, Surve V, Caballero J, et al. CaV2.3 calcium channels control second-phase insulin release. J Clin Invest. 2005;115:146-54 pubmed
    ..3(-/-) mouse. We propose a specific role for Ca(V)2.3 Ca(2+) channels in second-phase insulin release, that of mediating the Ca(2+) entry needed for replenishment of the releasable pool of granules as well as islet cell differentiation. ..
  34. Weiergräber M, Henry M, Ho M, Struck H, Hescheler J, Schneider T. Altered thalamocortical rhythmicity in Ca(v)2.3-deficient mice. Mol Cell Neurosci. 2008;39:605-18 pubmed publisher
    ..This study provides evidence for the first time that Ca(v)2.3 E/R-type Ca2+ channels are important in modulating thalamocortical hyperoscillation exerting anti-epileptogenic effects in non-convulsive absence seizures. ..
  35. Waka N, Knipper M, Engel J. Localization of the calcium channel subunits Cav1.2 (alpha1C) and Cav2.3 (alpha1E) in the mouse organ of Corti. Histol Histopathol. 2003;18:1115-23 pubmed publisher
    ..The immunohistochemical localization of Cav1.2 (alpha1C) and Cav2.3 (alpha1E) Ca2+ channels was studied in the developing and adult mouse organ of Corti using subunit-specific antibodies and ..
  36. Lu Z, Pereverzev A, Liu H, Weiergräber M, Henry M, Krieger A, et al. Arrhythmia in isolated prenatal hearts after ablation of the Cav2.3 (alpha1E) subunit of voltage-gated Ca2+ channels. Cell Physiol Biochem. 2004;14:11-22 pubmed
    ..3e as ion conducting pore stabilize a more regular heart beat in prenatal mice. ..
  37. Son W, Han C, Lee J, Jung K, Lee H, Choo Y. Developmental expression patterns of alpha1H T-type Ca2+ channels during spermatogenesis and organogenesis in mice. Dev Growth Differ. 2002;44:181-90 pubmed
    ..Transcripts of L-type (alpha1D), non-L-type (alpha1E) and T-type Ca2+ channels were detected in round spermatids...
  38. Lee S, Choi S, Lee T, Kim H, Chin H, Shin H. Molecular basis of R-type calcium channels in central amygdala neurons of the mouse. Proc Natl Acad Sci U S A. 2002;99:3276-81 pubmed
    ..Here we generated alpha1E-deficient mice (alpha1E-/-) and examined the status of voltage-sensitive Ca2+ currents in central amygdala (CeA) ..
  39. Suzuki T, Delgado Escueta A, Aguan K, Alonso M, Shi J, Hara Y, et al. Mutations in EFHC1 cause juvenile myoclonic epilepsy. Nat Genet. 2004;36:842-9 pubmed
    ..3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME. ..
  40. Saegusa H, Matsuda Y, Tanabe T. Effects of ablation of N- and R-type Ca(2+) channels on pain transmission. Neurosci Res. 2002;43:1-7 pubmed
    ..3-/- mice, was also observed in the Ca(v)2.2-/- mice. Therefore, it is suggested that these mutant mice could provide novel models to delineate the nociceptive and antinociceptive mechanisms. ..
  41. Zaman T, Zhou X, Pandey N, Qin Z, Keyhanian K, Wen K, et al. LMO4 is essential for paraventricular hypothalamic neuronal activity and calcium channel expression to prevent hyperphagia. J Neurosci. 2014;34:140-8 pubmed publisher
    ..Real-time PCR quantification revealed that LMO4 regulates the expression of Ca(2+) channels (Cacna1h, Cacna1e) that underlie neuronal excitability...
  42. 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
  43. Kubota M, Murakoshi T, Saegusa H, Kazuno A, Zong S, Hu Q, et al. Intact LTP and fear memory but impaired spatial memory in mice lacking Ca(v)2.3 (alpha(IE)) channel. Biochem Biophys Res Commun. 2001;282:242-8 pubmed
    ..3-/- mice, they displayed an obvious impairment in the probe test. These results suggest that the Ca(v)2.3 channel plays some role in formation of the accurate spatial memory but not of the fear memory. ..
  44. Wang K, Kelley M, Wu W, Adelman J, Maylie J. Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice. PLoS ONE. 2015;10:e0139332 pubmed publisher
    ..2-containing channels to CaV2.3 channels to provide negative feedback regulation of EPSPs in the spines of CA1 pyramidal neurons. ..
  45. Zhang J, Tan L, Ren Y, Liang J, Lin R, Feng Q, et al. Presynaptic Excitation via GABAB Receptors in Habenula Cholinergic Neurons Regulates Fear Memory Expression. Cell. 2016;166:716-728 pubmed publisher
    ..We identify the role of an extra-amygdalar circuit and presynaptic GABAB receptors in fear control, suggesting that boosting neurotransmission in this pathway might ameliorate some fear disorders. ..
  46. Parajuli L, Nakajima C, Kulik A, Matsui K, Schneider T, Shigemoto R, et al. Quantitative regional and ultrastructural localization of the Ca(v)2.3 subunit of R-type calcium channel in mouse brain. J Neurosci. 2012;32:13555-67 pubmed
    ..3 density was variable among similar-sized spine heads and did not correlate with the density in the parent dendrite, implying that spines are individual calcium compartments operating autonomously from their parent dendrites. ..
  47. Ricoy U, FRERKING M. Distinct roles for Cav2.1-2.3 in activity-dependent synaptic dynamics. J Neurophysiol. 2014;111:2404-13 pubmed publisher
    ..Thus different Cav2 channels vary in their coupling to synaptic transmission over different frequency ranges, with consequences for the frequency tuning of both synaptic dynamics and presynaptic neuromodulation. ..
  48. Weiergräber M, Henry M, Krieger A, Kamp M, Radhakrishnan K, Hescheler J, et al. Altered seizure susceptibility in mice lacking the Ca(v)2.3 E-type Ca2+ channel. Epilepsia. 2006;47:839-50 pubmed
    ..We provide novel insight into the functional involvement of Ca(v)2.3 in ictogenesis and seizure susceptibility on the whole-animal level. ..