Cacna1a

Summary

Gene Symbol: Cacna1a
Description: calcium voltage-gated channel subunit alpha1 A
Alias: BccA1, Cav2.1, rbA-1, voltage-dependent P/Q-type calcium channel subunit alpha-1A, RBA-I, brain calcium channel 1, brain calcium channel I, brain class A, calcium channel alpha 1A, calcium channel, L type, alpha-1 polypeptide, calcium channel, voltage-dependent, P/Q type, alpha 1A subunit, calcium channel, voltage-dependent, alpha 1A subunit, voltage-gated calcium channel subunit alpha Cav2.1
Species: rat
Products:     Cacna1a

Top Publications

  1. Zhou H, Yu K, McCoy K, Lee A. Molecular mechanism for divergent regulation of Cav1.2 Ca2+ channels by calmodulin and Ca2+-binding protein-1. J Biol Chem. 2005;280:29612-9 pubmed
    ..We conclude that the NT and IQ-domains of alpha(1)1.2 mediate functionally distinct interactions with CaBP1 and CaM that promote conformational alterations that either stabilize or inhibit inactivation of Ca(v)1.2. ..
  2. Kaeser P, Deng L, Wang Y, Dulubova I, Liu X, Rizo J, et al. RIM proteins tether Ca2+ channels to presynaptic active zones via a direct PDZ-domain interaction. Cell. 2011;144:282-95 pubmed publisher
    ..We propose that RIMs tether N- and P/Q-type Ca(2+) channels to presynaptic active zones via a direct PDZ-domain-mediated interaction, thereby enabling fast, synchronous triggering of neurotransmitter release at a synapse...
  3. Agler H, Evans J, Tay L, Anderson M, Colecraft H, Yue D. G protein-gated inhibitory module of N-type (ca(v)2.2) ca2+ channels. Neuron. 2005;46:891-904 pubmed
    ..Thus, an NT module, acting via interactions with the I-II loop, appears fundamental to such modulation. ..
  4. Berkefeld H, Sailer C, Bildl W, Rohde V, Thumfart J, Eble S, et al. BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling. Science. 2006;314:615-20 pubmed
    ..Complex formation with distinct Cav channels enables BKCa-mediated membrane hyperpolarization that controls neuronal firing pattern and release of hormones and transmitters in the central nervous system. ..
  5. Fletcher C, Tottene A, Lennon V, Wilson S, Dubel S, Paylor R, et al. Dystonia and cerebellar atrophy in Cacna1a null mice lacking P/Q calcium channel activity. FASEB J. 2001;15:1288-90 pubmed
  6. Catterall W. Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011;3:a003947 pubmed publisher
    ..This article presents the molecular relationships and physiological functions of these Ca(2+) channel proteins and provides information on their molecular, genetic, physiological, and pharmacological properties. ..
  7. 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. ..
  8. Scheuber A, Miles R, Poncer J. Presynaptic Cav2.1 and Cav2.2 differentially influence release dynamics at hippocampal excitatory synapses. J Neurosci. 2004;24:10402-9 pubmed
    ..2 by G(o/i), thereby increasing the number of available channels. ..
  9. Nimmrich V, Grimm C, Draguhn A, Barghorn S, Lehmann A, Schoemaker H, et al. Amyloid beta oligomers (A beta(1-42) globulomer) suppress spontaneous synaptic activity by inhibition of P/Q-type calcium currents. J Neurosci. 2008;28:788-97 pubmed publisher
    ..Selective enhancement of the P/Q calcium current may provide a promising strategy in the treatment of Alzheimer's disease. ..

More Information

Publications62

  1. Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton D, Amos C, et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet. 1997;15:62-9 pubmed
    ..We conclude that a small polyglutamine expansion in the human alpha 1A calcium channel is most likely the cause of a newly classified autosomal dominant spinocerebellar ataxia, SCA6. ..
  2. Jun K, Piedras Rentería E, Smith S, Wheeler D, Lee S, Lee T, et al. Ablation of P/Q-type Ca(2+) channel currents, altered synaptic transmission, and progressive ataxia in mice lacking the alpha(1A)-subunit. Proc Natl Acad Sci U S A. 1999;96:15245-50 pubmed
    ..The alpha(1A)(-/-) mice provide a starting point for unraveling neuropathological mechanisms of human diseases generated by mutations in alpha(1A). ..
  3. Few A, Lautermilch N, Westenbroek R, Scheuer T, Catterall W. Differential regulation of CaV2.1 channels by calcium-binding protein 1 and visinin-like protein-2 requires N-terminal myristoylation. J Neurosci. 2005;25:7071-80 pubmed
    ..Differential, myristoylation-dependent regulation of presynaptic Ca2+ channels by nCaBPs may provide a flexible mechanism for diverse forms of short-term synaptic plasticity. ..
  4. 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...
  5. Su X, Leon L, Laping N. Role of spinal Cav2.2 and Cav2.1 ion channels in bladder nociception. J Urol. 2008;179:2464-9 pubmed publisher
    ..However, agatoxin and verapamil were less effective. The study suggests that spinal Cav2.2 and Q-type Cav2.1 calcium channels contribute to acute bladder nociception, while Cav1 channels have a limited role. ..
  6. Wick P, Westenbroek R, Holz R. Effects of expression of a mouse brain L-type calcium channel alpha 1 subunit on secretion from bovine adrenal chromaffin cells. Mol Pharmacol. 1996;49:295-302 pubmed
  7. Ogasawara M, Kurihara T, Hu Q, Tanabe T. Characterization of acute somatosensory pain transmission in P/Q-type Ca(2+) channel mutant mice, leaner. FEBS Lett. 2001;508:181-6 pubmed
    ..These results suggest the critical importance of the P/Q-type channel in modulation of acute somatosensory pain transmission in spinal cord...
  8. Kinoshita K, Watanabe Y, Asai H, Yamamura M, Matsuoka Y. Anti-ataxic effects of TRH and its analogue, TA-0910, in Rolling mouse Nagoya by metabolic normalization of the ventral tegmental area. Br J Pharmacol. 1995;116:3274-8 pubmed
    ..4. These results suggest that the ataxia of the rolling mouse may be due to dysfunction of the cerebellum and VTA, and that amelioration by TRH and TA-0910 could result from metabolic normalization of the VTA. ..
  9. Wang D, Fisher T. Expression of CaV 2.2 and splice variants of CaV 2.1 in oxytocin- and vasopressin-releasing supraoptic neurones. J Neuroendocrinol. 2014;26:100-10 pubmed publisher
    ..1 in VP and OT MNCs, as well as the expression in MNCs of deletion variants of Ca(V)2.1 that do not interact with exocytotic proteins and therefore may be less likely to mediate exocytotic release. ..
  10. Kaunisto M, Harno H, Kallela M, Somer H, Sallinen R, Hamalainen E, et al. Novel splice site CACNA1A mutation causing episodic ataxia type 2. Neurogenetics. 2004;5:69-73 pubmed
    ..The disease is caused by mutations in the P/Q-type calcium channel Ca(v)2.1 subunit gene, CACNA1A, located on chromosome 19p13.2...
  11. Inchauspe C, Martini F, Forsythe I, Uchitel O. Functional compensation of P/Q by N-type channels blocks short-term plasticity at the calyx of Held presynaptic terminal. J Neurosci. 2004;24:10379-83 pubmed
    ..We conclude that one physiological function of P/Q channels is to provide additional facilitatory drive, so contributing to maintenance of transmission as vesicles are depleted during high throughput synaptic transmission. ..
  12. Grüsser Cornehls U, Luy M, Bäurle J. Electrophysiology and GABA-immunocytochemistry in the vestibular nuclei of normal (C57BL/6J) and Leaner mutant mice. Brain Res. 1995;703:51-62 pubmed
    ..These conditions may contribute, among others, to the severe motor disturbances in Leaner. ..
  13. Noebels J, Sidman R. Inherited epilepsy: spike-wave and focal motor seizures in the mutant mouse tottering. Science. 1979;204:1334-6 pubmed
    ..Metabolic activity was increased bilaterally in selected brainstem structures. Spontaneous electrocorticographic and clinical seizures of this general pattern were recognized hitherto only in humans. ..
  14. Starr T, Prystay W, Snutch T. Primary structure of a calcium channel that is highly expressed in the rat cerebellum. Proc Natl Acad Sci U S A. 1991;88:5621-5 pubmed
    ..We report here the isolation and characterization of cDNAs encoding the rat brain class A (rbA) Ca channel...
  15. Condliffe S, Fratangeli A, Munasinghe N, Saba E, Passafaro M, Montrasio C, et al. The E1015K variant in the synprint region of the CaV2.1 channel alters channel function and is associated with different migraine phenotypes. J Biol Chem. 2013;288:33873-83 pubmed publisher
    Mutations in the CACNA1A gene, which encodes the pore-forming ?1A subunit of the CaV2.1 voltage-gated calcium channel, cause a number of human neurologic diseases including familial hemiplegic migraine...
  16. Lee A, Westenbroek R, Haeseleer F, Palczewski K, Scheuer T, Catterall W. Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-binding protein 1. Nat Neurosci. 2002;5:210-7 pubmed
    ..Our results identify an interaction between Ca2+ channels and CaBP1 that may regulate Ca2+-dependent forms of synaptic plasticity by inhibiting Ca2+ influx into neurons. ..
  17. Chen Y, Zhou J, Xie N, Huang C, Zhang J, Hu Z, et al. Lowering glucose level elevates [Ca2+]i in hypothalamic arcuate nucleus NPY neurons through P/Q-type Ca2+ channel activation and GSK3? inhibition. Acta Pharmacol Sin. 2012;33:594-605 pubmed publisher
    ..Lowering glucose level enhances the activity of P/Q type Ca(2+)channels and elevates [Ca(2+)](i) level in hypothalamic arcuate nucleus neurons via inhibition of GSK3?. ..
  18. Plomp J, Vergouwe M, van den Maagdenberg A, Ferrari M, Frants R, Molenaar P. Abnormal transmitter release at neuromuscular junctions of mice carrying the tottering alpha(1A) Ca(2+) channel mutation. Brain. 2000;123 Pt 3:463-71 pubmed
    ..This study shows that functional consequences of alpha(1A) mutations causing cerebral disorders can be characterized at the NMJ. ..
  19. Matsui K, Masui A, Kato N, Adachi K. Levels of somatostatin and cholecystokinin in the brain of ataxic mutant mice. Life Sci. 1993;53:333-40 pubmed
    ..SOM and CCK-8 content (ng/organ) was significantly higher in PCD and RMN than in controls but this was not in the weaver mice. The possible involvement of both peptides in manifestations of ataxia is discussed. ..
  20. Caddick S, Wang C, Fletcher C, Jenkins N, Copeland N, Hosford D. Excitatory but not inhibitory synaptic transmission is reduced in lethargic (Cacnb4(lh)) and tottering (Cacna1atg) mouse thalami. J Neurophysiol. 1999;81:2066-74 pubmed
    ..This may be an important factor underlying the generation of seizures in these models...
  21. Nakayama T, Nagai Y. Alterations in local cerebral glucose metabolism and endogenous thyrotropin-releasing hormone levels in rolling mouse Nagoya and effect of thyrotropin-releasing hormone tartrate. Jpn J Pharmacol. 1996;72:241-6 pubmed
    ..These results suggest that ataxic symptoms in RMN (rol/rol) may relate to the abnormal metabolism of TRH and energy metabolism in the cerebellum and/or brain stem and that exogenously given TRH normalizes them. ..
  22. Ferron L, Nieto Rostro M, Cassidy J, Dolphin A. Fragile X mental retardation protein controls synaptic vesicle exocytosis by modulating N-type calcium channel density. Nat Commun. 2014;5:3628 pubmed publisher
    ..Finally, we show that FMRP controls synaptic exocytosis via Ca(V)2.2 channels. Our data indicate that FMRP is a potent regulator of presynaptic activity, and its loss is likely to contribute to synaptic dysfunction in FXS. ..
  23. Sasaki S, Huda K, Inoue T, Miyata M, Imoto K. Impaired feedforward inhibition of the thalamocortical projection in epileptic Ca2+ channel mutant mice, tottering. J Neurosci. 2006;26:3056-65 pubmed
  24. López Soto E, Agosti F, Cabral A, Mustafa E, Damonte V, Gandini M, et al. Constitutive and ghrelin-dependent GHSR1a activation impairs CaV2.1 and CaV2.2 currents in hypothalamic neurons. J Gen Physiol. 2015;146:205-19 pubmed publisher
  25. Tomoda H, Kato M, Sakata S, Shima F. Striatal dysfunction in Rolling mouse Nagoya: an electrophysiological study. J Neurol Sci. 1992;112:106-12 pubmed
    ..These results are in agreement with our previously reported findings of increased glucose metabolism and reduced concentration of GABA in the GP and substantia nigra pars reticula (SNr) in rolling.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  26. Kulik A, Nakadate K, Hagiwara A, Fukazawa Y, Lujan R, Saito H, et al. Immunocytochemical localization of the alpha 1A subunit of the P/Q-type calcium channel in the rat cerebellum. Eur J Neurosci. 2004;19:2169-78 pubmed
  27. Campbell D, Hess E. L-type calcium channels contribute to the tottering mouse dystonic episodes. Mol Pharmacol. 1999;55:23-31 pubmed
    ..The susceptibility of L-type calcium channels to voltage-dependent facilitation may promote this abnormal motor phenotype. ..
  28. Isaacs K, Abbott L. Cerebellar volume decreases in the tottering mouse are specific to the molecular layer. Brain Res Bull. 1995;36:309-14 pubmed
    ..The density of Purkinje cells and the total number of Purkinje cells did not vary between groups. The cerebellar and body weights were decreased in tg/tg and tg/tg(la) mice compared with +/+ mice. ..
  29. Meier H, MacPike A. Three syndromes produced by two mutant genes in the mouse. Clinical, pathological, and ultrastructural bases of tottering, leaner, and heterozygous mice. J Hered. 1971;62:297-302 pubmed
  30. Myojin K, Hiroi T, Ikeda H, Kodama H. Sulfur amino acid levels and related enzyme activities in various brain regions (and other tissues) in normal mice and rolling mice Nagoya. Acta Med Okayama. 1992;46:401-5 pubmed
    ..Cystathionine beta-synthase and cystathionine gamma-lyase activities in the liver, kidney, and pancreas were almost the same in both the normal mice and rolling mice Nagoya. ..
  31. Vigues S, Gastaldi M, Chabret C, Massacrier A, Cau P, Valmier J. Regulation of calcium channel alpha(1A) subunit splice variant mRNAs in kainate-induced temporal lobe epilepsy. Neurobiol Dis. 1999;6:288-301 pubmed
    ..The long-lasting changes in alpha(1A) subunit mRNA contents suggests that VGCC may be involved in the mechanisms generating chronic focal hyperexcitability and/or cellular damage in temporal lobe epilepsy. ..
  32. Fletcher C, Lutz C, O Sullivan T, Shaughnessy J, Hawkes R, Frankel W, et al. Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell. 1996;87:607-17 pubmed
    ..These studies define the first mutations in a mammalian central nervous system-specific voltage-sensitive calcium channel and identify the first gene involved in absence epilepsy. ..
  33. Koyanagi Y, Sawada K, Sakata Haga H, Jeong Y, Fukui Y. Increased serotonergic innervation of lumbosacral motoneurons of rolling mouse Nagoya in correlation with abnormal hindlimb extension. Anat Histol Embryol. 2006;35:387-92 pubmed
  34. Zwingman T, Neumann P, Noebels J, Herrup K. Rocker is a new variant of the voltage-dependent calcium channel gene Cacna1a. J Neurosci. 2001;21:1169-78 pubmed
    ..the rocker locus was mapped to mouse chromosome 8 within 2 centimorgans of the calcium channel alpha1a subunit (Cacna1a, formerly known as tottering) locus...
  35. Ishikawa K, Fujigasaki H, Saegusa H, Ohwada K, Fujita T, Iwamoto H, et al. Abundant expression and cytoplasmic aggregations of [alpha]1A voltage-dependent calcium channel protein associated with neurodegeneration in spinocerebellar ataxia type 6. Hum Mol Genet. 1999;8:1185-93 pubmed
    ..repeat expansion for this disease has been identified in the [alpha]1A voltage-dependent calcium channel gene (CACNA1A), the mechanism which leads to predominant Purkinje cell degeneration is totally unknown...
  36. Lorenzon N, Lutz C, Frankel W, Beam K. Altered calcium channel currents in Purkinje cells of the neurological mutant mouse leaner. J Neurosci. 1998;18:4482-9 pubmed
    ..Thus, the leaner mutation selectively reduces P-type currents in Purkinje cells, and the alpha1A subunit and P-type current appear to be essential for normal cerebellar function. ..
  37. Luvisetto S, Marinelli S, Panasiti M, D Amato F, Fletcher C, Pavone F, et al. Pain sensitivity in mice lacking the Ca(v)2.1alpha1 subunit of P/Q-type Ca2+ channels. Neuroscience. 2006;142:823-32 pubmed
    ..1 channels in central sensitization. ..
  38. Tokuda S, Kuramoto T, Tanaka K, Kaneko S, Takeuchi I, Sasa M, et al. The ataxic groggy rat has a missense mutation in the P/Q-type voltage-gated Ca2+ channel alpha1A subunit gene and exhibits absence seizures. Brain Res. 2007;1133:168-77 pubmed
    ..missense (M251K) mutation in the alpha(1A) subunit of the P/Q-type voltage-gated Ca(2+) channel gene (Cacna1a) within the gry-critical region...
  39. Prieto G, Pérez Burgos A, Palomero Rivero M, Galarraga E, Drucker Colín R, Bargas J. Upregulation of D2-class signaling in dopamine-denervated striatum is in part mediated by D3 receptors acting on Ca V 2.1 channels via PIP2 depletion. J Neurophysiol. 2011;105:2260-74 pubmed publisher
  40. Matsushita K, Wakamori M, Rhyu I, Arii T, Oda S, Mori Y, et al. Bidirectional alterations in cerebellar synaptic transmission of tottering and rolling Ca2+ channel mutant mice. J Neurosci. 2002;22:4388-98 pubmed
  41. Li D, Wang F, Lai M, Chen Y, Zhang J. A protein phosphatase 2calpha-Ca2+ channel complex for dephosphorylation of neuronal Ca2+ channels phosphorylated by protein kinase C. J Neurosci. 2005;25:1914-23 pubmed
    ..Thus, the PP2calpha-Ca2+ channel complex is responsible for rapid dephosphorylation of Ca2+ channels and may contribute to regulation of synaptic transmission in neurons. ..
  42. Chioza B, Wilkie H, Nashef L, Blower J, McCormick D, Sham P, et al. Association between the alpha(1a) calcium channel gene CACNA1A and idiopathic generalized epilepsy. Neurology. 2001;56:1245-6 pubmed
  43. Levitt P, Noebels J. Mutant mouse tottering: selective increase of locus ceruleus axons in a defined single-locus mutation. Proc Natl Acad Sci U S A. 1981;78:4630-4 pubmed
    ..These findings are consistent with a specific gene-linked alteration of developmental events controlling the number of axons produced by a single neuronal population in the mammalian brain. ..
  44. Muramoto O, Kanazawa I, Ando K. Neurotransmitter abnormality in Rolling mouse Nagoya, an ataxic mutant mouse. Brain Res. 1981;215:295-304 pubmed
  45. Isaacs K, Abbott L. Development of the paramedian lobule of the cerebellum in wild-type and tottering mice. Dev Neurosci. 1992;14:386-93 pubmed
  46. Miyazaki T, Hashimoto K, Shin H, Kano M, Watanabe M. P/Q-type Ca2+ channel alpha1A regulates synaptic competition on developing cerebellar Purkinje cells. J Neurosci. 2004;24:1734-43 pubmed
    ..This molecular function facilitates the distal extension of climbing fiber innervation along the dendritic tree of the Purkinje cell and also establishes climbing fiber monoinnervation of individual Purkinje cells. ..
  47. Green M, Sidman R. Tottering--a neuromusclar mutation in the mouse. And its linkage with oligosyndacylism. J Hered. 1962;53:233-7 pubmed
  48. Campbell D, North J, Hess E. Tottering mouse motor dysfunction is abolished on the Purkinje cell degeneration (pcd) mutant background. Exp Neurol. 1999;160:268-78 pubmed
    Tottering (tg) mice inherit a recessive mutation of the calcium channel alpha 1A subunit gene, which encodes the pore-forming protein of P/Q-type voltage-sensitive calcium channels and is predominantly expressed in cerebellar granule and ..
  49. Gandini M, Sandoval A, Zamponi G, Felix R. The MAP1B-LC1/UBE2L3 complex catalyzes degradation of cell surface CaV2.2 channels. Channels (Austin). 2014;8:452-7 pubmed publisher
    ..In addition, here we propose that this novel mechanism of CaV channel regulation might be conserved among N-type and P/Q-type channels. ..
  50. Yu A, Hebert S, Brenner B, Lytton J. Molecular characterization and nephron distribution of a family of transcripts encoding the pore-forming subunit of Ca2+ channels in the kidney. Proc Natl Acad Sci U S A. 1992;89:10494-8 pubmed
    ..One gene, CaCh4, is expressed primarily in the cortex, and by microdissected-tubule PCR was found predominantly in the distal convoluted tubule, consistent with a role in transepithelial Ca2+ reabsorption at this site. ..
  51. Macleod G, Chen L, Karunanithi S, Peloquin J, Atwood H, McRory J, et al. The Drosophila cacts2 mutation reduces presynaptic Ca2+ entry and defines an important element in Cav2.1 channel inactivation. Eur J Neurosci. 2006;23:3230-44 pubmed
    ..1 channel inactivation. ..
  52. Cavelier P, Beekenkamp H, Shin H, Jun K, Bossu J. Cerebellar slice cultures from mice lacking the P/Q calcium channel: electroresponsiveness of Purkinje cells. Neurosci Lett. 2002;333:64-8 pubmed
    ..These results confirm that P/Q Ca(2+) channels elicit Ca(2+)-dependent plateau potentials and control the propagation of the dendritic LTS to the soma. ..
  53. Tehrani M, Barnes E. Reduced function of gamma-aminobutyric acidA receptors in tottering mouse brain: role of cAMP-dependent protein kinase. Epilepsy Res. 1995;22:13-21 pubmed
    ..It is suggested that the resulting loss of inhibition could play a role in induction of the seizures which characterize the mutant phenotype. ..