CACNA1A

Summary

Gene Symbol: CACNA1A
Description: calcium voltage-gated channel subunit alpha1 A
Alias: APCA, CACNL1A4, CAV2.1, EA2, EIEE42, FHM, HPCA, MHP, MHP1, SCA6, voltage-dependent P/Q-type calcium channel subunit alpha-1A, brain calcium channel 1, brain calcium channel I, calcium channel, L type, alpha-1 polypeptide, calcium channel, voltage-dependent, P/Q type, alpha 1A subunit, fetal brain Ca2+ voltage-gated channel alpha1A pore-forming subunit, voltage-gated calcium channel subunit alpha Cav2.1
Species: human

Top Publications

  1. pmc Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-binding protein 1
    Amy Lee
    Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195 7280, USA
    Nat Neurosci 5:210-7. 2002
  2. ncbi Systematic identification of splice variants in human P/Q-type channel alpha1(2.1) subunits: implications for current density and Ca2+-dependent inactivation
    Tuck Wah Soong
    National Neuroscience Institute, Singapore 308433
    J Neurosci 22:10142-52. 2002
  3. ncbi Specific kinetic alterations of human CaV2.1 calcium channels produced by mutation S218L causing familial hemiplegic migraine and delayed cerebral edema and coma after minor head trauma
    Angelita Tottene
    Department of Biomedical Sciences, University of Padova, CNR Institute of Neuroscience, Viale G Colombo 3, 35121 Padova, Italy
    J Biol Chem 280:17678-86. 2005
  4. ncbi Endogenous and exogenous Ca2+ buffers differentially modulate Ca2+-dependent inactivation of Ca(v)2.1 Ca2+ channels
    Lisa Kreiner
    Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 281:4691-8. 2006
  5. pmc Modulation of CaV2.1 channels by Ca2+/calmodulin-dependent protein kinase II bound to the C-terminal domain
    Xin Jiang
    Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280, USA
    Proc Natl Acad Sci U S A 105:341-6. 2008
  6. ncbi CaV2.1 (P/Q channel) interaction with synaptic proteins is essential for depolarization-evoked release
    Moshe Cohen-Kutner
    Department of Biological Chemistry, The Silverman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Channels (Austin) 4:266-77. 2010
  7. pmc Splice isoform-specific suppression of the Cav2.1 variant underlying spinocerebellar ataxia type 6
    Wei Ling Tsou
    Institute of Neuroscience, School of Life Sciences, National Yang Ming University, Taipei, Taiwan
    Neurobiol Dis 43:533-42. 2011
  8. doi CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis
    Osvaldo D Uchitel
    Instituto de Fisiologia, Biología Molecular y Neurociencias CONICET, Departamento de Fisiologia, Biologia Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
    J Physiol Paris 106:12-22. 2012
  9. ncbi Gating deficiency in a familial hemiplegic migraine type 1 mutant P/Q-type calcium channel
    Curtis F Barrett
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA
    J Biol Chem 280:24064-71. 2005
  10. ncbi Detection of a novel missense mutation and second recurrent mutation in the CACNA1A gene in individuals with EA-2 and FHM
    K L Friend
    Department of Cytogenetics and Molecular Genetics Women s and Children s Hospital, North Adelaide, South Australia, Australia
    Hum Genet 105:261-5. 1999

Research Grants

  1. Spinocerebellar Ataxia Type 2 Gene and Gene Product
    Stefan M Pulst; Fiscal Year: 2012
  2. Principles of Therapy in Cerebellar Disease: Explorations in Ion Channel Mutants
    JOHN SAMUEL STAHL; Fiscal Year: 2013
  3. Kamran Khodakhah; Fiscal Year: 2016
  4. Splice isoform-specific RNAi as therapy for Spinocerebellar Ataxia type 6
    Edgardo Rodriguez; Fiscal Year: 2012
  5. Non-Invasive Quantitation of Cellular and Biochemical Changes in Hereditary Ataxi
    GULIN OZ; Fiscal Year: 2009
  6. William A Catterall; Fiscal Year: 2016
  7. FUNCTIONAL ANALYSIS OF CALCIUM CHANNEL MUTATIONS IN TRIGEMINAL NOCICEPTION
    Yuqing Cao; Fiscal Year: 2010
  8. William A Catterall; Fiscal Year: 2016
  9. Central Synaptic Transmission in Drosophila.
    DIANE O DOWD; Fiscal Year: 2009
  10. How Ephexin Signaling Promotes Neuronal Stability
    CARL ANDREW FRANK; Fiscal Year: 2012

Detail Information

Publications255 found, 100 shown here

  1. pmc Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-binding protein 1
    Amy Lee
    Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195 7280, USA
    Nat Neurosci 5:210-7. 2002
    ..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...
  2. ncbi Systematic identification of splice variants in human P/Q-type channel alpha1(2.1) subunits: implications for current density and Ca2+-dependent inactivation
    Tuck Wah Soong
    National Neuroscience Institute, Singapore 308433
    J Neurosci 22:10142-52. 2002
    ..These findings significantly expand the anticipated scope of functional diversity produced by splice variation of P/Q-type channels...
  3. ncbi Specific kinetic alterations of human CaV2.1 calcium channels produced by mutation S218L causing familial hemiplegic migraine and delayed cerebral edema and coma after minor head trauma
    Angelita Tottene
    Department of Biomedical Sciences, University of Padova, CNR Institute of Neuroscience, Viale G Colombo 3, 35121 Padova, Italy
    J Biol Chem 280:17678-86. 2005
    ..Ca(2+) channels produces a severe clinical phenotype in which typical attacks of familial hemiplegic migraine (FHM) triggered by minor head trauma are followed, after a lucid interval, by deep (even fatal) coma and long lasting ..
  4. ncbi Endogenous and exogenous Ca2+ buffers differentially modulate Ca2+-dependent inactivation of Ca(v)2.1 Ca2+ channels
    Lisa Kreiner
    Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 281:4691-8. 2006
    ..We conclude that Ca2+-dependent inactivation of Ca(v)2.1 depends on a subplasmalemmal Ca2+ microdomain that is affected by the amplitude of the Ca2+ current and differentially modulated by distinct Ca2+ buffers...
  5. pmc Modulation of CaV2.1 channels by Ca2+/calmodulin-dependent protein kinase II bound to the C-terminal domain
    Xin Jiang
    Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280, USA
    Proc Natl Acad Sci U S A 105:341-6. 2008
    ..This regulatory mechanism would be important in presynaptic nerve terminals, where Ca(V)2.1 channels initiate synaptic transmission and CaMKII has noncatalytic effects on presynaptic plasticity...
  6. ncbi CaV2.1 (P/Q channel) interaction with synaptic proteins is essential for depolarization-evoked release
    Moshe Cohen-Kutner
    Department of Biological Chemistry, The Silverman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Channels (Austin) 4:266-77. 2010
    ....
  7. pmc Splice isoform-specific suppression of the Cav2.1 variant underlying spinocerebellar ataxia type 6
    Wei Ling Tsou
    Institute of Neuroscience, School of Life Sciences, National Yang Ming University, Taipei, Taiwan
    Neurobiol Dis 43:533-42. 2011
    ..1 voltage-gated calcium channel subunit (CACNA1A)...
  8. doi CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis
    Osvaldo D Uchitel
    Instituto de Fisiologia, Biología Molecular y Neurociencias CONICET, Departamento de Fisiologia, Biologia Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
    J Physiol Paris 106:12-22. 2012
    ....
  9. ncbi Gating deficiency in a familial hemiplegic migraine type 1 mutant P/Q-type calcium channel
    Curtis F Barrett
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA
    J Biol Chem 280:24064-71. 2005
    ..This identification of an intrinsic defect in FHM1 mutant channels helps explain their impact on neurotransmission when they occupy type-specific slots for P/Q channels at central nerve terminals...
  10. ncbi Detection of a novel missense mutation and second recurrent mutation in the CACNA1A gene in individuals with EA-2 and FHM
    K L Friend
    Department of Cytogenetics and Molecular Genetics Women s and Children s Hospital, North Adelaide, South Australia, Australia
    Hum Genet 105:261-5. 1999
    Mutations in the brain specific P/Q type Ca2+ channel alpha1 subunit gene, CACNA1A, have been identified in three clinically distinct disorders, viz...
  11. pmc Complete loss of P/Q calcium channel activity caused by a CACNA1A missense mutation carried by patients with episodic ataxia type 2
    S Guida
    Department of Biology, Tor Vergata University, Rome, Italy
    Am J Hum Genet 68:759-64. 2001
    ..hemiplegic migraine, episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6 are allelic disorders of the CACNA1A gene (coding for the alpha(1A) subunit of P/Q calcium channels), usually associated with different types of ..
  12. doi CACNA1A nonsense mutation is associated with basilar-type migraine and episodic ataxia type 2
    Matthew S Robbins
    The Montefiore Headache Center, Saul R Korey Department of Neurology, Albert Einstein College of Medicine, 1575 Blondell Avenue, Suite 225, Bronx, NY 10461, USA
    Headache 49:1042-6. 2009
    Mutations in the CACNA1A gene on chromosome 19 have been associated with a variety of clinical disorders, including familial hemiplegic migraine type 1 and episodic ataxia type 2 (EA2)...
  13. ncbi Late-onset episodic ataxia type 2 due to an in-frame insertion in CACNA1A
    P Imbrici
    Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, United Kingdom
    Neurology 65:944-6. 2005
    Episodic ataxia type 2 (EA2) is caused by calcium channel (CACNA1A) mutations and typically begins before age 20 years. The molecular basis of late-onset EA2 is unclear...
  14. ncbi Calcium-binding protein 1 is an inhibitor of agonist-evoked, inositol 1,4,5-trisphosphate-mediated calcium signaling
    Lee P Haynes
    The Physiological Laboratory, Crown Street, University of Liverpool, Liverpool L69 3BX, UK
    J Biol Chem 279:547-55. 2004
    ..Together, these data suggest that L-CaBP1 is able to specifically regulate InsP3 receptor-mediated alterations in [Ca2+]i during agonist stimulation...
  15. doi Premature stop codons in a facilitating EF-hand splice variant of CaV2.1 cause episodic ataxia type 2
    Tracey D Graves
    Institute of Neurology, University College London, Queen Square, London, United Kingdom
    Neurobiol Dis 32:10-5. 2008
    Premature stop codons in CACNA1A, which encodes the alpha(1A) subunit of neuronal P/Q-type (Ca(V)2.1) Ca(2+) channels, cause episodic ataxia type 2 (EA2)...
  16. ncbi Internuclear ophthalmoparesis in episodic ataxia type 2
    Janet C Rucker
    Neurology Service, Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, OH 44106 1702, USA
    Ann N Y Acad Sci 1039:571-4. 2005
    Two patients sharing a novel mutation of the CACNA1A gene for P/Q calcium channels showed significant slowing of adducting saccades compared with normal subjects or patients with cerebellar disease...
  17. ncbi G protein-gated inhibitory module of N-type (ca(v)2.2) ca2+ channels
    Heather L Agler
    Department of Biomedical Engineering and Ca2 Signals Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Neuron 46:891-904. 2005
    ..Thus, an NT module, acting via interactions with the I-II loop, appears fundamental to such modulation...
  18. ncbi Dominant-negative effects of human P/Q-type Ca2+ channel mutations associated with episodic ataxia type 2
    Chung Jiuan Jeng
    School of Medicine, Fu Jen Catholic University, Hsin Chuang, Taipei County, Taiwan
    Am J Physiol Cell Physiol 290:C1209-20. 2006
    Episodic ataxia type 2 (EA2) is an inherited autosomal dominant disorder related to cerebellar dysfunction and is associated with mutations in the pore-forming alpha(1A)-subunits of human P/Q-type Ca(2+) channels (Cav2.1 channels)...
  19. ncbi Dominant-negative effects of episodic ataxia type 2 mutations involve disruption of membrane trafficking of human P/Q-type Ca2+ channels
    Chung Jiuan Jeng
    Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei, Taiwan
    J Cell Physiol 214:422-33. 2008
    Episodic ataxia type 2 (EA2) is an autosomal dominant neurological disorder associated with mutations in the gene encoding pore-forming alpha(1A) subunits of human P/Q-type calcium (Ca(V)2.1) channels...
  20. ncbi Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel
    E Perez-Reyes
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030
    J Biol Chem 267:1792-7. 1992
    ..These results indicate that the cardiac L-type Ca2+ channel has a similar subunit structure as in skeletal muscle, and provides evidence for the modulatory role of the beta subunit...
  21. ncbi Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4
    R A Ophoff
    MGC Department of Human Genetics, Sylvius Laboratory, Leiden University, The Netherlands
    Cell 87:543-52. 1996
    ..We characterized a brain-specific P/Q-type Ca2+ channel alpha1-subunit gene, CACNL1A4, covering 300 kb with 47 exons...
  22. ncbi Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel
    O Zhuchenko
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    Nat Genet 15:62-9. 1997
    ..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.
  23. ncbi Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p
    C Jodice
    Dipartimento di Biologia, Universita di Tor Vergata, Rome, Italy
    Hum Mol Genet 6:1973-8. 1997
    Point mutations of the CACNA1A gene coding for the alpha 1A voltage-dependent calcium channel subunit are responsible for familial hemiplegic migraine (FHM) and episodic ataxia type 2 (EA2)...
  24. pmc Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1
    K Ishikawa
    Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, Japan
    Am J Hum Genet 61:336-46. 1997
    ..Analysis of CAG-repeat expansion in the alpha1A-voltage-dependent calcium channel (CACNL1A4) gene lying in 19p13...
  25. ncbi A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit
    D Walker
    INSERM U464, Institut Federatif Jean Roche, Faculte de Medecine Nord, Marseille, France
    J Biol Chem 273:2361-7. 1998
    ..This is the first demonstration of a molecular basis for the specificity of functional effects seen for different combinations of these two channel components...
  26. ncbi A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation
    D Walker
    INSERM Unité 464, Institut Federatif Jean Roche, Faculte de Medecine Nord, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France
    J Biol Chem 274:12383-90. 1999
    ..Our data contribute to our understanding of the molecular organization of calcium channels, providing a functional basis for variation in subunit composition of native P/Q-type channels...
  27. ncbi Spinocerebellar ataxia type 6 mutation alters P-type calcium channel function
    S Toru
    Department of Neurology and Neurological Science, Japan
    J Biol Chem 275:10893-8. 2000
    ..On the other hand, other types of neurons, expressing both alpha1A(-NP) and alpha1A(+NP), may survive because the positive shift of voltage-dependent inactivation of alpha1A(+NP) compensates Ca(2+) influx...
  28. pmc Familial hemiplegic migraine mutations increase Ca(2+) influx through single human CaV2.1 channels and decrease maximal CaV2.1 current density in neurons
    Angelita Tottene
    Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy
    Proc Natl Acad Sci U S A 99:13284-9. 2002
    ..1 channels containing mutations linked to familial hemiplegic migraine (FHM). Here, we extend the previous single-channel analysis to human Ca(V)2.1 channels containing mutation V1457L...
  29. ncbi A novel insertion mutation of acetazolamide-responsive episodic ataxia in a Japanese family
    Zenjiro Matsuyama
    Department of Neurology and Geriatrics, Gifu University, School of Medicine, Tsukasa machi, Gifu 500 8705, Japan
    J Neurol Sci 210:91-3. 2003
    ..These episodes usually lasted for several hours two or three times a week. Direct sequence of CACNA1A demonstrated a novel insertion mutation in the patient and her father...
  30. ncbi A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression
    Arn M J M van den Maagdenberg
    Department of Biomedical Sciences, University of Padova, CNR Institute of Neuroscience, Viale G Colombo 3, 35121 Padova, Italy
    Neuron 41:701-10. 2004
    ..migraine type 1 (FHM-1) is a Mendelian subtype of migraine with aura that is caused by missense mutations in the CACNA1A gene that encodes the alpha(1) subunit of neuronal Ca(v)2.1 Ca(2+) channels...
  31. ncbi Alternative splicing as a molecular switch for Ca2+/calmodulin-dependent facilitation of P/Q-type Ca2+ channels
    Dipayan Chaudhuri
    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 24:6334-42. 2004
    ..The physiological function of these variants is likely important, because we find that the distribution of EF-hand splice variants is strikingly heterogeneous in the human brain, varying both across regions and during development...
  32. ncbi A clinical and genetic study in a large cohort of patients with spinocerebellar ataxia type 6
    Hiroki Takahashi
    Department of Neurology and Neurological Science, Tokyo Medical and Dental University Graduate School of Medicine, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8519, Japan
    J Hum Genet 49:256-64. 2004
    In order to clarify the clinical and genetic features of SCA6, we retrospectively analyzed 140 patients...
  33. ncbi Familial hemiplegic migraine type 1 mutations K1336E, W1684R, and V1696I alter Cav2.1 Ca2+ channel gating: evidence for beta-subunit isoform-specific effects
    Carmen Mullner
    Abteilung Pharmakologie und Toxikologie, Institut fur Pharmazie, Universitat Innsbruck, Peter Mayrstrasse 1 I, A 6020 Innsbruck, Austria
    J Biol Chem 279:51844-50. 2004
    ..As the beta-subunit composition of Cav2.1 channels varies in different brain regions, our data predict that the functional FHM1 phenotype also varies between different neurons or even within different neuronal compartments...
  34. pmc Modal gating of human CaV2.1 (P/Q-type) calcium channels: I. The slow and the fast gating modes and their modulation by beta subunits
    Siro Luvisetto
    Dept of Biomedical Sciences, University of Padova, Viale G Colombo 3, 35121 Padova, Italy
    J Gen Physiol 124:445-61. 2004
    ....
  35. ncbi New calcium channel mutations predict aberrant RNA splicing in episodic ataxia
    Louise H Eunson
    Department of Molecular Neurosciences, Institute of Neurology, University College London, London, UK
    Neurology 65:308-10. 2005
    ..EA2 cases are associated with mutations in the alpha1A subunit of the P/Q-type voltage-gated calcium channel gene CACNA1A. In a UK national study, the authors analyzed 15 index cases with typical EA2 and identified two unreported ..
  36. ncbi C-termini of P/Q-type Ca2+ channel alpha1A subunits translocate to nuclei and promote polyglutamine-mediated toxicity
    Holly B Kordasiewicz
    Department of Neuroscience, Unviersity of Minnesota, 420 Delaware Street SE, Minneapolis, 55455, USA
    Hum Mol Genet 15:1587-99. 2006
    ..The C-terminal fragment bears a polyglutamine tract which, when expanded (Q33) as in spinocerebellar ataxia type 6 (SCA6), is toxic to cells. Moreover, polyglutamine-mediated toxicity is dependent on nuclear localization...
  37. doi Large CACNA1A deletion in a family with episodic ataxia type 2
    Florence Riant
    Laboratoire de Genetique, Groupe Hospitalier Lariboisière Fernand Widal, Groupement Hospitalier Universitaire Nord, Assistance Publique Hopitaux de Paris, 2 rue Ambroise Pare, 75010 Paris, France
    Arch Neurol 65:817-20. 2008
    ..Episodic ataxia type 2 (EA2) is characterized by prolonged episodes of ataxia with interictal nystagmus and is caused by mutations in CACNA1A. All mutations identified thus far (to our knowledge) are nonsense or missense point mutations.
  38. ncbi Ca(V)2.1 P/Q-type calcium channel alternative splicing affects the functional impact of familial hemiplegic migraine mutations: implications for calcium channelopathies
    Paul J Adams
    Michael Smith Laboratories, University of British Columbia, Vancouver, BC, CA
    Channels (Austin) 3:110-21. 2009
    ..the present study, we systematically compare the biophysical effects of three type-1 familial hemiplegic migraine (FHM-1) mutations in two predominant splice variants of the neuronal Ca(V)2.1 P/Q-type channel...
  39. doi Large scale calcium channel gene rearrangements in episodic ataxia and hemiplegic migraine: implications for diagnostic testing
    R W Labrum
    MRC Centre for Neuromuscular Diseases, Institute of Neurology, UCL, London WC1N 3BG, UK
    J Med Genet 46:786-91. 2009
    ..Point mutations in CACNA1A, which encodes the neuronal P/Q-type calcium channel, have been detected in many cases of EA2 and FHM1...
  40. doi Identification of CACNA1A large deletions in four patients with episodic ataxia
    Florence Riant
    AP HP, Groupe Hospitalier Lariboisière Fernand Widal, Laboratoire de Genetique, GHU Nord, Paris, France
    Neurogenetics 11:101-6. 2010
    ..Episodic ataxia type 2 (EA2) is caused by mutations in CACNA1A. EA2 mutations are mostly nonsense and sometimes missense mutations...
  41. pmc The carboxy-terminal fragment of alpha(1A) calcium channel preferentially aggregates in the cytoplasm of human spinocerebellar ataxia type 6 Purkinje cells
    Taro Ishiguro
    Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8519, Japan
    Acta Neuropathol 119:447-64. 2010
    Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative disease caused by a small polyglutamine (polyQ) expansion (control: 4-20Q; SCA6: 20-33Q) in the carboxyl(C)-terminal cytoplasmic domain of the alpha(1A) ..
  42. doi Identification of novel and recurrent CACNA1A gene mutations in fifteen patients with episodic ataxia type 2
    Elide Mantuano
    Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy
    J Neurol Sci 291:30-6. 2010
    ..The disease was caused by mutations in the CACNA1A gene, on chromosome 19p. We perform a mutational screening in a group of 43 unrelated patients...
  43. pmc Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential
    Carlota Gonzalez Inchauspe
    Instituto de Fisiologia, Biología Molecular y Neurociencias, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Departamento de Fisiologia, Biologia Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
    J Neurophysiol 104:291-9. 2010
    Familial hemiplegic migraine type-1 FHM-1 is caused by missense mutations in the CACNA1A gene that encodes the alpha(1A) pore-forming subunit of Ca(V)2.1 Ca(2+) channels...
  44. doi A wide spectrum of clinical, neurophysiological and neuroradiological abnormalities in a family with a novel CACNA1A mutation
    Romina Romaniello
    Department Child Neuropsychiatry and Neurorehabilitation IRCCS, E Medea Scientific Institute, Bosisio Parini, Lecco, Italy
    J Neurol Neurosurg Psychiatry 81:840-3. 2010
    Mutations in the calcium channel voltage dependent P/Q-type alpha-1A subunit (CACNA1A) can cause different neurological disorders which share a wide range of symptoms, including episodic ataxia type 2 (EA2), familial hemiplegic migraine (..
  45. doi The Cavβ subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channels
    Christophe Altier
    Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
    Nat Neurosci 14:173-80. 2011
    ..Thus, Cavββ regulates the ubiquitination and stability of the calcium channel complex...
  46. pmc Molecular determinants of CaV2.1 channel regulation by calcium-binding protein-1
    Alexandra P Few
    Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195 7280, USA
    J Biol Chem 286:41917-23. 2011
    ..1 channels by CaBP1. These findings give insight into the molecular code by which CaS proteins differentially regulate Ca(V)2.1 channel function and provide diversity of form and function of short term synaptic plasticity...
  47. ncbi Proteolytic cleavage and cellular toxicity of the human alpha1A calcium channel in spinocerebellar ataxia type 6
    Takayuki Kubodera
    Department of Neurology and Neurological Science, Graduate School of Medicine, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8519, Japan
    Neurosci Lett 341:74-8. 2003
    Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease caused by small CAG repeat expansion in the alpha1A calcium channel gene...
  48. ncbi Polyglutamine repeats of spinocerebellar ataxia 6 impair the cell-death-preventing effect of CaV2.1 Ca2+ channel--loss-of-function cellular model of SCA6
    Zenjiro Matsuyama
    Department of Neurology and Geriatrics Gifu University, Graduate School of Medicine, Gifu 501 1194, Japan
    Neurobiol Dis 17:198-204. 2004
    ..To elucidate the pathogenic mechanisms underlying SCA6, we introduced CAG repeats of various lengths into the Ca2+ channel alpha12...
  49. pmc Modal gating of human CaV2.1 (P/Q-type) calcium channels: II. the b mode and reversible uncoupling of inactivation
    Tommaso Fellin
    Dept of Biomedical Sciences, University of Padova, Viale G Colombo, 3 35121 Padova, Italy
    J Gen Physiol 124:463-74. 2004
    ..1 channels could be a potent and versatile mechanism for the modulation of synaptic strength and plasticity as well as of neuronal excitability and other postsynaptic Ca2+-dependent processes...
  50. pmc Elementary mechanisms producing facilitation of Cav2.1 (P/Q-type) channels
    Dipayan Chaudhuri
    Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    J Gen Physiol 129:385-401. 2007
    ..This enhanced-opening mechanism suggests that the CDF evoked during action-potential trains would produce not only larger, but longer-lasting Ca(2+) responses, an outcome with potential ramifications for short-term synaptic plasticity...
  51. ncbi Wolff Award 1997. Involvement of a Ca2+ channel gene in familial hemiplegic migraine and migraine with and without aura. Dutch Migraine Genetics Research Group
    R A Ophoff
    MGC-Department of Human Genetics, Sylvius Laboratory, Leiden (The Netherlands) University, The Netherlands
    Headache 37:479-85. 1997
    ..This finding may provide a rationale for the development of specific prophylactic therapy for migraine and other (paroxysmal) cerebral disorders...
  52. pmc Differential regulation of Purkinje cell dendritic spines in rolling mouse Nagoya (tg/tg), P/Q type calcium channel (α1(A)/Ca(v)2.1) mutant
    Sen ich Oda
    Laboratory of Animal Management, School of Agricultural Science, Nagoya University, Nagoya, Japan
    Anat Cell Biol 43:211-7. 2010
    Voltage dependent calcium channels (VDCC) participate in regulation of neuronal Ca(2+). The Rolling mouse Nagoya (Cacna1a(tg-rol)) is a spontaneous P/Q type VDCC mutant, which has been suggested as an animal model for some human ..
  53. ncbi The Cav2.1/alpha1A (P/Q-type) voltage-dependent calcium channel mediates inhibitory neurotransmission onto mouse cerebellar Purkinje cells
    G J Stephens
    Neuronal Excitability Group, Biochemistry and Biophysics, Imperial College of Science, Technology and Medicine, London, SW7 2BZ, UK
    Eur J Neurosci 13:1902-12. 2001
    ..Electrophysiological and immunostaining data support a predominant role for Cav2.1 subunits in mediating action potential-evoked inhibitory GABA release onto mouse Purkinje cells...
  54. ncbi Forward genetic screen of mouse reveals dominant missense mutation in the P/Q-type voltage-dependent calcium channel, CACNA1A
    G Xie
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
    Genes Brain Behav 6:717-27. 2007
    Dominant mutations of the P/Q-type Ca(2+) channel (CACNA1A) underlie several human neurological disorders, including episodic ataxia type 2, familial hemiplegic migraine 1 (FHM1) and spinocerebellar ataxia 6, but have not been found ..
  55. ncbi The calcium channel alpha2delta-2 subunit partitions with CaV2.1 into lipid rafts in cerebellum: implications for localization and function
    Anthony Davies
    Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom
    J Neurosci 26:8748-57. 2006
    ..Together, these results indicate that both alpha2delta-2 and CaV2.1 are normally associated with cholesterol-rich microdomains, and this influences their functionality...
  56. ncbi The P/Q-type voltage-dependent calcium channel as pharmacological target in spinocerebellar ataxia type 6: gabapentin and pregabalin may be of therapeutic benefit
    José Gazulla
    Department of Neurology, Miguel Servet University Hospital, Zaragoza, Spain
    Med Hypotheses 68:131-6. 2007
    ..The alpha1A subunit, encoded by the CACNA1A gene, is the pore-forming subunit specific to the neuronal P/Q-type VDCCs...
  57. pmc Human neuronal stargazin-like proteins, gamma2, gamma3 and gamma4; an investigation of their specific localization in human brain and their influence on CaV2.1 voltage-dependent calcium channels expressed in Xenopus oocytes
    Fraser J Moss
    Department of Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK
    BMC Neurosci 4:23. 2003
    ..In addition, we investigated whether human gamma2 or gamma4 could modulate the electrophysiological properties of a neuronal VDCC complex transiently expressed in Xenopus oocytes...
  58. pmc Comparison of an expanded ataxia interactome with patient medical records reveals a relationship between macular degeneration and ataxia
    Juliette J Kahle
    Department of Cellular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Hum Mol Genet 20:510-27. 2011
    ..SCA7) are neurodegenerative disorders caused by expansion of CAG repeats encoding polyglutamine (polyQ) tracts in CACNA1A, the alpha1A subunit of the P/Q-type calcium channel, and ataxin-7 (ATXN7), a component of a chromatin-remodeling ..
  59. ncbi Clinical and molecular correlations in spinocerebellar ataxia type 6: a study of 24 Dutch families
    R J Sinke
    Department of Medical Genetics, University Medical Center Utrecht, KC04 084 2, PO Box 85090, 3508 AB Utrecht, The Netherlands
    Arch Neurol 58:1839-44. 2001
    ..Mild CAG repeat expansions in the alpha(1A) voltage-dependent calcium channel gene are associated with SCA type 6 (SCA6).
  60. doi Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms
    T Schmitz-Hübsch
    Department of Neurology, University Hospital of Bonn, Bonn, Germany
    Neurology 71:982-9. 2008
    To identify factors that determine disease severity and clinical phenotype of the most common spinocerebellar ataxias (SCAs), we studied 526 patients with SCA1, SCA2, SCA3. or SCA6.
  61. ncbi A new CACNA1A gene mutation in acetazolamide-responsive familial hemiplegic migraine and ataxia
    S Battistini
    Institute of Neurological Sciences, University of Siena, Italy
    Neurology 53:38-43. 1999
    To search for mutations in the calcium channel gene CACNA1A and to study the genotype-phenotype correlation in a family with a severe familial hemiplegic migraine (FHM) phenotype and a slowly progressive cerebellar ataxia.
  62. pmc Recurrence of the T666M calcium channel CACNA1A gene mutation in familial hemiplegic migraine with progressive cerebellar ataxia
    A Ducros
    Institut National de la Santé et de la Recherche Médicale INSERM U25, Faculte de Medecine Necker, 75730 Paris Cedex 15, France
    Am J Hum Genet 64:89-98. 1999
    ..In 20% of HM families, HM is associated with a mild permanent cerebellar ataxia (PCA). The CACNA1A gene encoding the alpha1A subunit of P/Q-type voltage-gated calcium channels is involved in 50% of unselected HM ..
  63. doi Visualization, quantification and correlation of brain atrophy with clinical symptoms in spinocerebellar ataxia types 1, 3 and 6
    Jorg B Schulz
    Department of Neurodegeneration and Restorative Research, Center for Neurological Medicine, University of Gottingen, Gottingen, Germany
    Neuroimage 49:158-68. 2010
    ..We therefore aimed to visualize, quantify and correlate localized brain atrophy with clinical symptoms in SCA1, SCA3, and SCA6.
  64. doi Severity and progression rate of cerebellar ataxia in 16q-linked autosomal dominant cerebellar ataxia (16q-ADCA) in the endemic Nagano Area of Japan
    Kunihiro Yoshida
    Department of Medicine Neurology and Rheumatology, Shinshu University School of Medicine, Asahi, Matsumoto, Japan
    Cerebellum 8:46-51. 2009
    ..Nagano, the central mountainous district of the main island of Japan, 16q-ADCA and spinocerebellar ataxia type 6 (SCA6) are the most and second most prevalent subtypes of ADCA, respectively...
  65. pmc Spinocerebellar ataxia type 6: genotype and phenotype in German kindreds
    L Schols
    Department of Neurology, St Josef Hospital, Ruhr University, Bochum, Germany
    J Neurol Neurosurg Psychiatry 64:67-73. 1998
    Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar ataxia (ADCA) of which the mutation causing the disease has recently been characterised as an expanded CAG trinucleotide repeat in the gene coding for the alpha1A-..
  66. ncbi Molecular pathogenesis of spinocerebellar ataxia type 6
    Holly B Kordasiewicz
    Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, California 92093, USA
    Neurotherapeutics 4:285-94. 2007
    ..is a neurodegenerative disorder caused by abnormal expansions of a trinucleotide CAG repeat in exon 47 of the CACNA1A gene, which encodes the alpha1A subunit of the P/Q-type voltage-gated calcium channel...
  67. ncbi Thermoregulation, gas exchange, and ventilation in Adelie penguins (Pygoscelis adeliae)
    M A Chappell
    Department of Biology, University of California, Riverside 92521
    J Comp Physiol B 157:783-90. 1988
    ..007 kg) was 0.0112 ml/[g.min], equivalent to a metabolic heat production (MHP) of 14.9 Watt. The respiratory exchange ratio was approximately 0.7 at all Ta...
  68. ncbi Prolonged cortical silent period but normal sensorimotor plasticity in spinocerebellar ataxia 6
    James T H Teo
    Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom
    Mov Disord 23:378-85. 2008
    Spinocerebellar ataxia 6 (SCA6) is a hereditary disease characterized by a trinucleotide repeat expansion in the CACNA1A gene and late-onset bilateral cerebellar atrophy...
  69. ncbi Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds
    B Tang
    Department of Neurology, Xiangya Hospital, Hunan Medical University, People s Republic of China
    Arch Neurol 57:540-4. 2000
    ..of SCA1 (spinocerebellar ataxia type 1), SCA2, SCA3/MJD (spinocerebellar ataxia type 3/Machado-Joseph disease), SCA6, SCA7, and DRPLA (dentatorubropallidoluysian atrophy) CAG trinucleotide repeat expansions [(CAG)n] among persons ..
  70. ncbi Degeneration of the inferior olive in spinocerebellar ataxia 6 may depend on disease duration: report of two autopsy cases and statistical analysis of autopsy cases reported to date
    Kuniaki Tsuchiya
    Department of Laboratory Medicine and Pathology, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan
    Neuropathology 25:125-35. 2005
    This report concerns a clinicopathological study of two autopsied patients with spinocerebellar ataxia 6 (SCA6), and a statistical analysis between neuronal loss of the inferior olive and disease duration of 15 SCA6 autopsy cases reported ..
  71. doi Vertigo and vestibular abnormalities in spinocerebellar ataxia type 6
    Patrick Yu-Wai-Man
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    J Neurol 256:78-82. 2009
    Spinocerebellar ataxia type 6 (SCA6) is a calcium channelopathy due to a pathological CAG repeat expansion in CACNL1A4. Patients frequently describe paroxysmal vertigo early in the disease course, but it is not clear whether this is ..
  72. ncbi Frequency of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Australian patients with spinocerebellar ataxia
    E Storey
    Van Cleef Roet Centre for Nervous Diseases, Alfred Hospital Monash University, Prahran, Victoria, Australia
    Am J Med Genet 95:351-7. 2000
    ..Of 88 pedigrees with multiple-affected members, SCA type 1 (SCA1) accounted for 16%, SCA2 for 6%, SCA3 for 12%, SCA6 for 17%, SCA7 for 2%, and 47% (41 pedigrees) were negative for each of SCA1, 2, 3, and 6...
  73. doi A neuropathological study at autopsy of early onset spinocerebellar ataxia 6
    XueJing Wang
    Department of Neurology, Xiangya Hospital, Central South University, Xiangya Road, Changsha, Hunan 410008, PR China
    J Clin Neurosci 17:751-5. 2010
    Spinocerebellar ataxia type 6 (SCA6) is a late-onset, autosomal dominantly inherited ataxic disorder, and most previous clinical studies consider SCA6 to be a "pure" cerebellar ataxia...
  74. ncbi Dopamine transporter positron emission tomography in spinocerebellar ataxias type 1, 2, 3, and 6
    Ullrich Wullner
    Department of Neurology, University of Bonn, Bonn, Germany
    Arch Neurol 62:1280-5. 2005
    ..group of autosomal dominant ataxias: some mutations, including SCA1, SCA2, and SCA3, are multisystemic disorders characterized by a variety of noncerebellar symptoms while others, like SCA6, give rise to a pure cerebellar syndrome.
  75. ncbi [Spinocerebellar ataxias in infancy: pathogenesis of potassium and calcium channels' diseases, clinical features and therapeutical approach]
    E Bozzola
    Dipartimento di Scienze Pediatriche, Fondazione IRCCS San Matteo, Pavia, Italy
    Minerva Pediatr 59:149-56. 2007
    ..EA2 can result from mutations in the CACNA1A gene, encoding calcium channels on chromosome 19p13...
  76. pmc High germinal instability of the (CTG)n at the SCA8 locus of both expanded and normal alleles
    I Silveira
    UnIGENe, IBMC, 4150 180 Porto, Portugal
    Am J Hum Genet 66:830-40. 2000
    ..The mutant proteins have shown an expanded polyglutamine tract in SCA1, SCA2, MJD/SCA3, SCA6, SCA7, and DRPLA; a glycine-to-arginine substitution was found in SCA6 as well...
  77. doi Deficit of heat shock transcription factor 1-heat shock 70 kDa protein 1A axis determines the cell death vulnerability in a model of spinocerebellar ataxia type 6
    Li Li
    Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
    Genes Cells 14:1253-69. 2009
    Spinocerebellar ataxia type 6 (SCA6) is caused by a small expansion of polyglutamine (polyQ)-encoding CAG repeat in Ca(v)2.1 calcium channel gene...
  78. doi The wide clinical spectrum and nigrostriatal dopaminergic damage in spinocerebellar ataxia type 6
    Jong Min Kim
    Seoul National University Hospital, Department of Neurology, Chongno Ku Yunkeun Dong 28, Seoul 110 744, South Korea
    J Neurol Neurosurg Psychiatry 81:529-32. 2010
    Spinocerebellar ataxia type 6 (SCA6) manifests a wide spectrum of non-cerebellar system involvements. The objective of this study was to examine the presence of nigrostriatal dopaminergic system derangement in SCA6...
  79. ncbi Influence of interleukin-1beta gene polymorphism on age-at-onset of spinocerebellar ataxia 6 (SCA6) in Japanese patients
    M Nishimura
    Department of Neurology and Clinical Research Center, Utano National Hospital, 616 8255, Kyoto, Japan
    Neurosci Lett 307:128-30. 2001
    ..correlation is observed between the expanded CAG repeat number and age-at-onset of spinocerebellar ataxia 6 (SCA6)...
  80. doi Frequencies of spinocerebellar ataxia subtypes in Thailand: window to the population history?
    Thanyachai Sura
    Division of Medical Genetics and Molecular Medicine, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
    J Hum Genet 54:284-8. 2009
    ..We searched for SCA type 1, SCA2, SCA3, SCA6, SCA7 and dentatorubral-pallidoluysian atrophy mutations using GeneScan analysis in 340 patients from 182 families, ..
  81. ncbi In vivo selection of Enterobacter aerogenes with reduced susceptibility to cefepime and carbapenems associated with decreased expression of a 40 kDa outer membrane protein and hyperproduction of AmpC beta-lactamase
    Felipe Fernandez-Cuenca
    Department of Microbiology, University of Seville, and University Hospital Virgen Macarena, Seville, Spain
    Int J Antimicrob Agents 27:549-52. 2006
    ..to cefepime (FEP) and/or imipenem (IMP) in three consecutive isolates of Enterobacter aerogenes (Ea1, Ea2 and Ea3) cultured from bronchial aspirates of the same patient after treatment with ceftriaxone and FEP were ..
  82. ncbi Frequency analysis and clinical characterization of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Korean patients
    Won Yong Lee
    Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    Arch Neurol 60:858-63. 2003
    ..Despite the genetic differentiation of SCA, the characterization of the phenotypes of various SCAs has been challenging for better clinical diagnosis...
  83. ncbi Eyeblink conditioning in patients with hereditary ataxia: a one-year follow-up study
    D Timmann
    Department of Neurology, University of Duisburg Essen, Hufelandstrasse 55, 45122, Essen, Germany
    Exp Brain Res 162:332-45. 2005
    ..24 patients with spinocerebellar ataxia type 6 (SCA6), type 3 (SCA3), and Friedreich's ataxia (FRDA) participated...
  84. ncbi Clinical spectrum of episodic ataxia type 2
    J Jen
    UCLA Neurology, 90095 1769, USA
    Neurology 62:17-22. 2004
    The authors searched for mutations in CACNA1A in patients with episodic ataxia and describe the clinical spectrum in genetically defined patients...
  85. ncbi Prognostic value of auto-antibodies in the serum of Omani patients with gastric cancer
    Ahmed Al-Shukaili
    Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, PO Box 35, PC 123, Muscat, Sultanate of Oman
    Saudi Med J 27:1873-7. 2006
    ..To investigate the prevalence of a group of different autoantibodies, in Omani patients with gastric cancer, and to examine whether their presence correlates with clinical course of the disease...
  86. ncbi Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families
    Alfredo Brusco
    Dipartimento di Genetica, Biologia e Biochimica, Università di Torino and Unitá Operativa Genetica Medica, Ospedale San Giovanni Battista di Torino, Torino, Italy
    Arch Neurol 61:727-33. 2004
    ..The relevant gene has been identified in 12 cases (SCA1-3, SCA6-8, SCA10, SCA12, FGF14, and DRPLA), and in all but the recently identified SCA14, SCA17, PRKCG and FGF14 genes, the ..
  87. pmc Genetic and functional characterisation of the P/Q calcium channel in episodic ataxia with epilepsy
    Sanjeev Rajakulendran
    MRC Centre for Neuromuscular Diseases, Department of Molecular Neuroscience, University College London, Institute of Neurology, London WC1N 3BG, UK
    J Physiol 588:1905-13. 2010
    Mutations in CACNA1A, which encodes the principal subunit of the P/Q calcium channel, underlie episodic ataxia type 2 (EA2)...
  88. pmc Neuropsychological features of patients with spinocerebellar ataxia (SCA) types 1, 2, 3, and 6
    Ina Klinke
    Department of Epileptology, University of Bonn, Bonn, Germany
    Cerebellum 9:433-42. 2010
    ..Thirty-two SCA patients (SCA1, 6; SC2, 3; SCA3, 15; SCA6, 8) and 14 matched healthy controls underwent neuropsychological evaluation testing attention, executive functions, ..
  89. ncbi Perinatal periods of risk: analysis of fetal-infant mortality rates in Kansas City, Missouri
    Jinwen Cai
    Kansas City Health Department, Office of Epidemiology and Community Health Monitoring, Kansas City, MS, USA
    Matern Child Health J 9:199-205. 2005
    ..Results offer important information that can be used to develop community-based prevention strategies related to racial/ethnic disparities in infant mortality rates (IMR)...
  90. pmc The therapeutic mode of action of 4-aminopyridine in cerebellar ataxia
    Karina Alviña
    Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Neurosci 30:7258-68. 2010
    Episodic ataxia type 2 (EA2) is a hereditary cerebellar ataxia associated with mutations in the P/Q-type voltage-gated calcium (Ca(2+)) channels. Therapeutic approaches for treatment of EA2 are very limited...
  91. ncbi [Lung pathology of complex congenital heart defect with diminished pulmonary blood flow but without aortopulmonary collateral artery and patent ductus arteriosus in infants and young children]
    Xiao Tong Zhang
    Center of Pediatric Cardiac Surgery, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing 100037, China
    Zhongguo Dang Dai Er Ke Za Zhi 10:311-4. 2008
    ..changes of small pulmonary arteries and alveoli in complex congenital heart defect with diminished pulmonary blood flow but without aortopulmonary collateral artery (APCA) and patent ductus arteriosus (PDA) in infants and young children.
  92. ncbi A novel nonsense mutation in CACNA1A causes episodic ataxia and hemiplegia
    J Jen
    Department of Neurology, University of California at Los Angeles School of Medicine, 90095 1769, USA
    Neurology 53:34-7. 1999
    ..To identify the disease-causing mutation and to characterize penetrance and phenotypic variability in a large pedigree with episodic ataxia type 2 (EA-2) previously linked to chromosome 19...
  93. ncbi Assessment of distribution of CD34 epitope classes in fresh and cryopreserved peripheral blood progenitor cells and acute myeloid leukemic blasts
    F Lanza
    Hematology Section, Dept of Biomedical Sciences and Advanced Therapies, University of Ferrara, St Anna Hospital, Corso Giovecca 203, 44100 Ferrara, Italy E mail
    Haematologica 84:969-77. 1999
    ..However, there are no data on the effects of cryopreservation on the expression of the three CD34 epitope classes, and on their relationship with the clonogenic capacity of PBPC collected by leukapheresis...
  94. ncbi Alternative splicing generates a smaller assortment of CaV2.1 transcripts in cerebellar Purkinje cells than in the cerebellum
    Srinivasan Kanumilli
    Department of Pharmacology, University of Bristol, Bristol, United Kingdom
    Physiol Genomics 24:86-96. 2006
    P/Q-type calcium channels control many calcium-driven functions in the brain. The CACNA1A gene encoding the pore-forming CaV2.1 (alpha1A) subunit of P/Q-type channels undergoes alternative splicing at multiple loci...
  95. ncbi [Interaction mechanism of marine birnavirus (MABV) in fish cell lines]
    Syun ichirou Oshima
    Laboratory of Cell Structure and Function, Division of Marine Bioresource Science, Graduate School of Kuroshio Science, Kochi University, Japan
    Uirusu 55:133-44. 2005
    ..MABV adsorbed not only onto the cell surfaces of susceptible (CHSE-214 and RSBK-2) cells but also onto resistant (FHM and EPC) cells...
  96. pmc Contribution of calcium-dependent facilitation to synaptic plasticity revealed by migraine mutations in the P/Q-type calcium channel
    Paul J Adams
    Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada V6T 1Z4
    Proc Natl Acad Sci U S A 107:18694-9. 2010
    ..and native preparations, gain-of-function missense mutations underlying Familial Hemiplegic Migraine type 1 (FHM-1) occlude CDF of P/Q-type Ca(2+) channels...
  97. ncbi Edwardsiella ictaluri invasion of IEC-6, Henle 407, fathead minnow and channel catfish enteric epithelial cells
    Ramona T Skirpstunas
    Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164, USA
    Dis Aquat Organ 51:161-7. 2002
    ..rat small intestinal epithelium), Henle 407 (origin: human embryonic intestinal epithelium), fathead minnow (FHM, minnow epithelial cells) and trypsin/pepsin-harvested channel catfish enteric epithelial cells...
  98. pmc Delayed postnatal loss of P/Q-type calcium channels recapitulates the absence epilepsy, dyskinesia, and ataxia phenotypes of genomic Cacna1a mutations
    Melanie D Mark
    Department of Zoology and Neurobiology, ND7 31, Ruhr University Bochum, D 44780 Bochum, Germany
    J Neurosci 31:4311-26. 2011
    ..and dissect their role in neuronal networks at distinct developmental stages, we created a novel conditional Cacna1a knock-in mouse by inserting the floxed green fluorescent protein derivative Citrine into the first exon of ..
  99. ncbi Proton magnetic resonance spectroscopic imaging reveals differences in spinocerebellar ataxia types 2 and 6
    S M Boesch
    Department of Neurology, University of Innsbruck, Austria
    J Magn Reson Imaging 13:553-9. 2001
    ..resonance spectroscopy imaging (1H-MRSI) was performed in 4 patients with SCA2, and 3 patients carrying the SCA6 mutation...
  100. ncbi The voltage-gated calcium channel UNC-2 is involved in stress-mediated regulation of tryptophan hydroxylase
    Miguel Estevez
    Veterans Administration Hospital Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    J Neurochem 88:102-13. 2004
    ..is related to deficiency of serotonin signaling and abnormal function of the P/Q-type calcium channel, CACNA1A. Because the relationship of the CACNA1A channel to serotonin signaling is unknown and potentially of therapeutic ..
  101. doi Infantile nystagmus and late onset ataxia associated with a CACNA1A mutation in the intracellular loop between s4 and s5 of domain 3
    J Self
    Southampton Eye Unit, Southampton General Hospital, Southampton, UK
    Eye (Lond) 23:2251-5. 2009
    Mutations in the 1A-subunit of the brain P/Q-type calcium channel gene CACNA1A are responsible for spinocerebellar ataxia type 6 (SCA6), familial haemiplegic migraine (FHM) and episodic ataxia type 2 (EA2)...

Research Grants67

  1. Spinocerebellar Ataxia Type 2 Gene and Gene Product
    Stefan M Pulst; Fiscal Year: 2012
    ..In the previous funding period we defined the calcium channel subunit CACNA1A (Cav2.1) and the parkin E3 ubiquitin ligase as modifiers of the SCA2 phenotype in vitro and in humans...
  2. Principles of Therapy in Cerebellar Disease: Explorations in Ion Channel Mutants
    JOHN SAMUEL STAHL; Fiscal Year: 2013
    ..We focus on ocular motility abnormalities in mice carrying mutations of the CACNA1A gene of the P/Q (CaV2...
  3. Kamran Khodakhah; Fiscal Year: 2016
    ..Episodic ataxia type 2 (EA2), a hereditary ataxia caused by mutations in the P/Q-type calcium channels, is one such disorder...
  4. Splice isoform-specific RNAi as therapy for Spinocerebellar Ataxia type 6
    Edgardo Rodriguez; Fiscal Year: 2012
    ..1 calcium channel gene, CACNA1a. Selective loss of cerebellar Purkinje neurons is the pathological hallmark of SCA6, a slowly progressive and ..
  5. Non-Invasive Quantitation of Cellular and Biochemical Changes in Hereditary Ataxi
    GULIN OZ; Fiscal Year: 2009
    ..be quantified by high field (4 tesla) MRS in cerebella and pons of patients with spinocerebellar ataxias SCA2 and SCA6 in comparison to healthy controls...
  6. William A Catterall; Fiscal Year: 2016
    ..These studies will increase understanding of regulation of the heart by the sympathetic nervous system and give essential new insight into the molecular and functional changes in the Cav1.2 signaling complex in heart failure. ..
  7. FUNCTIONAL ANALYSIS OF CALCIUM CHANNEL MUTATIONS IN TRIGEMINAL NOCICEPTION
    Yuqing Cao; Fiscal Year: 2010
    ..Understanding the mechanisms of migraine will lead to more specific treatments. Familial Hemiplegic Migraine (FHM), a rare hereditary form of migraine with aura and hemiparesis, serves as a good model for exploring migraine ..
  8. William A Catterall; Fiscal Year: 2016
    ..This information will be essential to understanding of failure of spatial learning and memory in aging and disease. ..
  9. Central Synaptic Transmission in Drosophila.
    DIANE O DOWD; Fiscal Year: 2009
    ..Mutations in the CACNA1A gene, the human homolog of cac, are linked to neurological diseases that are characterized by a broad spectrum of ..
  10. How Ephexin Signaling Promotes Neuronal Stability
    CARL ANDREW FRANK; Fiscal Year: 2012
    ..TRAINEES: New recruited members of my laboratory will be trained in all aspects of this project. Over the course of three years, this may include a technician, two graduate students, and a postdoctoral fellow. ..
  11. Role of the Olivo-Cerebellar Network in Motor Coordination and Learning
    Rodolfo R Llinas; Fiscal Year: 2011
    ..Indeed, octanol, a specific blocker of CaV3.1 in the IO neurons is presently being considered for therapeutic use in this neurological condition in humans. ..
  12. GULIN OZ; Fiscal Year: 2014
    ..with SCAs and transgenic mouse models of SCA type 1 (SCA1) with excellent reproducibility;2) SCA1, SCA2 and SCA6 can be distinguished by neurochemical signatures;3) alterations in MRS biomarkers correlate cross-sectionally with ..
  13. Jerry L Prince; Fiscal Year: 2015
    ..Specific hypotheses related to patterns of degeneration and corresponding functional deficits in SCA2, SCA3, and SCA6 will be tested, and a preliminary map of the topography of functional scores on a low- dimensional shape space ..
  14. Sex differences in episodic neurologic disease
    HYDER JINNAH; Fiscal Year: 2009
    ..Rocker mice carry a mutation in Cacna1a, an autosomal gene that encodes a key subunit of the CaV2.1 voltage-regulated calcium channel...
  15. Targeting and function of presynaptic Ca2+ channels
    Stefan Herlitze; Fiscal Year: 2005
    ..and biophysical properties of wild type and mutated Ca2+ channels responsible for spinocerebellar ataxia 6 (SCA6) phenotypes effect synaptic transmission...
  16. Ocular motor control and MRI in hereditary ataxia
    Sarah Ying; Fiscal Year: 2009
    ..clinical presentation, functional measures of eye movements, and morphometry for two model populations, SCA2 and SCA6, which are genetically-defined cerebellar ataxia syndromes with complementary ocular motor phenotypes...
  17. Optogenetic modulation of episodic dystonia in the tottering mouse
    Samuel W Cramer; Fiscal Year: 2013
    ..importance to human diseases such as Episodic Ataxia type 2;a human channelopathy caused by mutations of the CACNA1A gene that encodes the human Cav2.1 (P/Q-type) voltage gated Ca2+ channel...
  18. Calcium Channels and Hereditary Ataxia
    Christopher Gomez; Fiscal Year: 2004
    ..The P/Q a subunit (a1A) encoded by the gene, CACNA1A, has been implicated in familial migraine, hereditary episodic ataxia and spinocerebellar ataxia type 6 (SCA6)...
  19. PATHOGENESIS STUDIES OF SPINOCEREBELLAR ATAXIA TYPE 6
    Cheng Lee; Fiscal Year: 2001
    DESCRIPTION (from Abstract): Recently, we made the discovery that Spinocerebellar ataxia type 6 (SCA6) is caused by a small polyglutamine tract expansion in the human (IA voltage gated calcium channel...
  20. Conformational Changes Underlying Intracellular Gating of the Leucine Transporter
    Kelli Kazmier; Fiscal Year: 2012
    ..The design of these aims will test the hypothesis, supported by the hydrantoin transporter (Mhp1) family of structures, that LeuT functions by a rocker switch mechanism...
  21. Andras Perl; Fiscal Year: 2016
    ..e., mitochondrial hyperpolarization (MHP), and, secondly, also ATP depletion, which are early and reversible steps of T-cell activation and apoptosis...
  22. Lisa Mosconi; Fiscal Year: 2014
    ..as the tracer (FDG-PET), we demonstrated that NL elderly with a maternal history of AD (FHm) show reductions in the cerebral metabolic rate of glucose (CMRglc) as compared to those with a paternal history of ..
  23. Properties of calcium channel mutants linked to migraine
    Yuqing Cao; Fiscal Year: 2004
    ..1), the pore-forming subunit of P/Q type calcium channel, are the leading cause of familial hemiplegic migraine (FHM), a rare, autosomal dominant form of migraine that provides an intriguing model for understanding other forms of ..
  24. Neural &Vascular Dysfunction As Mechanisms of Injury in Genetic Migraine Models
    Cenk Ayata; Fiscal Year: 2012
    ....
  25. Conformal, Portable External Fetal Heart Monitor
    Martin Culjat; Fiscal Year: 2011
    External fetal heart monitors (FHM) allow for intermittent or continuous monitoring of fetal status both before and during labor, and reduce medical costs by allowing fewer nurses or midwives to manage a larger number patients...
  26. Jeffrey Noebels; Fiscal Year: 2016
    ..In specific aim 1, new information from a conditional Cacna1a allele indicates that mice display SW epilepsy even when the P/Q type calcium current defects are engineered to ..
  27. Understanding the Mechanisms of Neuropathogenesis
    MICHAEL JOHN PALLADINO; Fiscal Year: 2010
    ..Na/K ATPase mutations cause Rapid-onset Dystonia Parkinsonism (RDP) and familial hemiplegic migraines (FHM)...
  28. MIGRAINE DRUG PROPHYLAXIS
    Michael Moskowitz; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  29. MULTI-EPITOPE MELANOMA VACCINES FOR CD4 AND CD8 T-CELLS
    Craig Slingluff; Fiscal Year: 2009
    ..advanced melanoma will be randomized to one of 4 vaccine strategies: (a) 12MP only, (b) 12MP + tet, (c) 12MP + 6 MHP, and (d) 6MHP only...
  30. Nervous System Channelopathies: Pathogenesis & Treatment
    ROBERT GRIGGS; Fiscal Year: 2005
    ..is no established treatment and there have been no well-designed clinical trials; (3) the episodic ataxias EA1 and EA2 for which treatment is not yet defined...
  31. Regulation of neuronal calcium channels by CaBP1
    Amy Lee; Fiscal Year: 2007
    ..RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page .................................................................................................................................................. ] Description, ..
  32. SMOKING ONSET IN A BIETHNIC POPULATION
    Leslie Robinson; Fiscal Year: 2005
    ..in mind, we propose the following Specific Aims: (1) To track participants of the Memphis Health Project (MHP), a study that has followed primarily low income, minority youth since the 7th grade (participants are now in 12th ..
  33. Service Use by Men on Methadone Commiting Partner Abuse
    Elwin Wu; Fiscal Year: 2003
    ..The proposed research will build upon findings from the Men's Health Project (MHP), an ongoing NIDA-funded study (PI: El-Bassel) to examine over time the relationships among drug abuse, IPV, and ..
  34. Central Synaptic Transmission in Drosophila.
    DIANE K O apos DOWD; Fiscal Year: 2010
    ..Mutations in the CACNA1A gene, the human homolog of cac, are linked to neurological diseases that are characterized by a broad spectrum of ..
  35. Genetics of Familial Episodic Ataxia
    Joanna C Jen; Fiscal Year: 2010
    ..We have expanded the clinical and genetic spectrum of EA2 and EA1, defined a new syndrome EA6, and mapped EA7...
  36. Pathobiology of Retinal Vasculopathy with Cerebal Leukodystrophy (RVCL)
    Joanna C Jen; Fiscal Year: 2010
    ..abstract_text> ..
  37. THE GENETIC & FUNCTIONAL ANATOMICAL BASIS OF HGPPS
    Joanna Jen; Fiscal Year: 2009
    ..Understanding the anatomical and molecular basis of HGPPS will provide insight into the genetically programmed neurodevelopment of the conjugate horizontal gaze center and other cranial nuclei in the brainstem. ..
  38. MUTATIONS IN CALCIUM CHANNELS CAUSING VERTIGO AND ATAXIA
    Joanna Jen; Fiscal Year: 2002
    The experiments outlined in this proposal seek to investigate how mutations in CACNL1A4, which encodes a brain calcium channel subunit, lead to symptoms of episodic vertigo and ataxia in familial hemiplegic migraine (FHM), episodic ataxia ..
  39. International Conference on Episodic Ataxia Syndromes
    Joanna Jen; Fiscal Year: 2005
    ..abstract_text> ..
  40. How Ephexin Signaling Promotes Neuronal Stability
    Carl Frank; Fiscal Year: 2009
    ..This proposal is designed to clarify exactly how Ephexin performs this function;the results may ultimately lead to a better understanding of the cause, progression, and treatment of neural diseases. ..
  41. Family History of Alzheimer's, Hypometabolism and Oxidative Stress
    Lisa Mosconi; Fiscal Year: 2009
    ..cognitively NL 65-80 year-old subjects, divided into 3 demographically matched groups of subjects with maternal (FHm) and paternal (FHp) family history of AD, and negative family history of AD (FH-)...
  42. CaM and nCaBP modulation of Cav2.1 and neurotransmission
    ALEXANDRA FEW; Fiscal Year: 2007
    ..This work will elucidate important signaling mechanisms contributing to short-term synaptic plasticity, which plays an important role in tuning network properties. [unreadable] [unreadable]..
  43. Denver Black Church Inititiative on Cancer
    Alfred Marcus; Fiscal Year: 2007
    ..research between the award winning Metro Denver Black Church Initiative (MDBCI), Faith & Health Ministries (FHM), and an outstanding group of senior behavioral scientists drawn from the AMC Cancer Research Center, as well as ..
  44. DIZZINESS IN OLDER PEOPLE
    Robert Baloh; Fiscal Year: 2006
    ..By continuing this longitudinal study of carefully studied older patients and controls, our multidisciplinary research team is in a good position to achieve our goals. ..
  45. Diseases of the Vestibular System
    Robert Baloh; Fiscal Year: 2006
    ..abstract_text> ..
  46. Vestibulocerebellar function in channelopathy mutants
    John Stahl; Fiscal Year: 2004
    ..Thus, the insights into normal cerebellar function generated by this study should also advance our understanding of mechanisms of heritable neurological disease. ..
  47. MOLECULAR BIOLOGY OF TRANSALDOLASE
    Andras Perl; Fiscal Year: 2004
    ..The proposed studies with the availability of unique reagents and existing model systems will further our knowledge on the role of TAL in the PPP, apoptosis signaling, and related disease processes. ..
  48. Mitochondrial dysfunction in patients with SLE
    Andras Perl; Fiscal Year: 2004
    ..Thus, checkpoints of mitochondrial hyperpolarization could represent novel targets of pharmacological intervention in patients with SLE. ..
  49. Confocal Microscope for Mutant-GFP-Based FRET
    David Yue; Fiscal Year: 2002
    ..The microscope will anchor a departmental facility supported by 3 major and 3 minor users, all of whose research would be fundamentally advanced by the platform's unique capabilities. ..
  50. CA CHANNELS: G PROTEINS & INACTIVATION
    David Yue; Fiscal Year: 2001
    ..Overall, this proposal will usher in new awareness and understanding of the potential role of Ca channels in short term changes of synaptic efficacy. ..
  51. IL10 and IGF1 Receptor Axis in Prostate Cancer
    Mark Stearns; Fiscal Year: 2005
    ..e. HPCA-10c cells immortalized with the telomerase gene)...
  52. Molecular Biology of Calcuim Channel Gamma Subunits
    Daniel Burgess; Fiscal Year: 2006
    ....
  53. Genetic and Immunological Impact of the HRES-1/Rab4 Locus in SLE
    Andras Perl; Fiscal Year: 2008
    ..Under Specific Aim 3, we will test the hypothesis that the HindIIIG653C allele, alone or in combination with other genetic factors of lupus-associated haplotypes, enhances the expression of HRES-1/Rab4. ..
  54. IL-10 Regulation of Lymphangiogenesis in Prostate Cancer
    Mark Stearns; Fiscal Year: 2008
    ..to block microvessel formation, prostate tumor growth and localized metastases by primary prostate tumor sublines, HPCA-10a, 10b, 10c, 10d, 10e and 10f...
  55. To study the neuronal mechanism of acupunture analgesia
    Albert Leung; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  56. Screen:Blockers of a CaV2.2-Mint-PDZ1 association (RMI)
    Ilya Bezprozvanny; Fiscal Year: 2004
    ..Biological activity of compounds identified in the full HTS screen will be tested in whole animal pain assays (formalin, hot plate, tail flick). ..
  57. Presenilins and neuronal calcium signaling
    ILYA B BEZPROZVANNY; Fiscal Year: 2010
    ..These data will also help to evaluate "Ca2+ hypothesis of AD" and will contribute to selecting optimal strategies for treatment of AD. ..
  58. A Mouse Model of RNA-induced Neurotoxcity
    Russell Margolis; Fiscal Year: 2008
    ..Finding the points of pathogenic convergence in these diseases may provide novel leads for the development of rational therapeutics. ..
  59. INTERACTIONS OF CALCIUM CHANNELS WITH ADAPTOR PROTEINS
    Ilya Bezprozvanny; Fiscal Year: 2003
    ..of polyglutamine repeat expansion in a1A sequence, which has been linked to autosomal dominant cerebellar ataxia (SCA6) disorder in humans...
  60. Generation of a mouse model of episodic ataxia type 2 (EA2)
    ELLEN HESS; Fiscal Year: 2008
    ..EA2 is caused by mutations in the CACNA1A gene, which encodes the pore-forming a12.1 subunit of Cav2.1 (P/Q-type) voltage-gated calcium channels...
  61. Parkin Interacting Proteins
    Stefan Pulst; Fiscal Year: 2006
    ..The ultimate goal of this R21 proposal is to further characterize proteins involved in parkin function and to screen these proteins for mutations or susceptibility alleles in PD patients. [unreadable] [unreadable]..
  62. Collaborative Care Approach for Children with ADHD
    James Guevara; Fiscal Year: 2007
    ..In the third study, a multifaceted collaborative care intervention for children with ADHD will be developed and piloted in an urban predominately African-American clinical setting. ..
  63. MOLECULAR GENETICS OF THE SCA1 LOCUS
    Harry Orr; Fiscal Year: 2003
    ..Understanding the importance of these factors for SCA1 pathogenesis should provide insights for polyglutamine diseases in general. ..
  64. Stigma & Behavioral Health in Urban Employers from China & US
    Patrick Corrigan; Fiscal Year: 2007
    ..Data from this study will be especially important for the development of future stigma-change programs. ..
  65. 2008 Calcium Signaling and Disease SGP Conference
    Ilya Bezprozvanny; Fiscal Year: 2008
    ..The major purpose of the SGP is to host a symposium each year on a different subject of wide interest to cell biologists, physiologists and biophysicists. [unreadable] [unreadable] [unreadable]..
  66. TRINUCLEOTIDE REPEATS AND NEUROLOGIC DISEASE
    Russell Margolis; Fiscal Year: 2004
    ..Overall, the proposed experiments will enable a systematic test for CAG/CTG expansion mutations in a variety of devastating neurodegenerative diseases. ..
  67. Examining the Gating Mechanisms of the Large-Conductance Ca2+ -activated K+ Chann
    DANIEL HENRY COX; Fiscal Year: 2010
    ..As the work proposed here is designed to uncover the natural mechanisms by which this channel is stimulated to open, it may very well point the way to the development of such beneficial pharmaceuticals. ..