CACNA1C

Summary

Gene Symbol: CACNA1C
Description: calcium voltage-gated channel subunit alpha1 C
Alias: CACH2, CACN2, CACNL1A1, CCHL1A1, CaV1.2, LQT8, voltage-dependent L-type calcium channel subunit alpha-1C, DHPR, alpha-1 subunit, calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle, calcium channel, cardic dihydropyridine-sensitive, alpha-1 subunit, calcium channel, voltage-dependent, L type, alpha 1C subunit, voltage-dependent L-type Ca2+ channel alpha 1 subunit, voltage-gated L-type calcium channel Cav1.2 alpha 1 subunit, splice variant 10*
Species: human

Top Publications

  1. pmc Structural basis for the differential effects of CaBP1 and calmodulin on Ca(V)1.2 calcium-dependent inactivation
    Felix Findeisen
    Cardiovascular Research Institute, University of California, San Francisco, CA 94158 2330, USA
    Structure 18:1617-31. 2010
  2. ncbi Molecular mechanism for divergent regulation of Cav1.2 Ca2+ channels by calmodulin and Ca2+-binding protein-1
    Hong Zhou
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 280:29612-9. 2005
  3. doi Hallmarks of the channelopathies associated with L-type calcium channels: a focus on the Timothy mutations in Ca(v)1.2 channels
    Isabelle Bidaud
    CNRS, UMR 5203, Institut de Genomique Fonctionnelle, Montpellier, France
    Biochimie 93:2080-6. 2011
  4. ncbi Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with Cav1.2 (L-type) Ca2+ channels
    Hong Zhou
    Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Neurosci 24:4698-708. 2004
  5. ncbi alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive calcium regulation
    Greg L Lyford
    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA
    Am J Physiol Cell Physiol 283:C1001-8. 2002
  6. doi Mapping of dihydropyridine binding residues in a less sensitive invertebrate L-type calcium channel (LCa v 1)
    Adriano Senatore
    Department of Biology, University of Waterloo, Waterloo, Ontario, Canada
    Channels (Austin) 5:173-87. 2011
  7. pmc Ca(v)1.2 splice variant with exon 9* is critical for regulation of cerebral artery diameter
    Matthew A Nystoriak
    Department of Pharmacology and Surgery, University of Vermont, College of Medicine, Burlington, VT 05405 0068, USA
    Am J Physiol Heart Circ Physiol 297:H1820-8. 2009
  8. ncbi Normalization of current kinetics by interaction between the alpha 1 and beta subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel
    A E Lacerda
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030
    Nature 352:527-30. 1991
  9. pmc Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart
    D Schultz
    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267 0575
    Proc Natl Acad Sci U S A 90:6228-32. 1993
  10. ncbi Tissue-specific expression of two human Ca(v)1.2 isoforms under the control of distinct 5' flanking regulatory elements
    Li Pang
    Department of Medicine, Montreal Heart Institute, and University of Montreal, 5000 Belanger St East, Montreal, QC, Canada H1T 1C8
    FEBS Lett 546:349-54. 2003

Detail Information

Publications241 found, 100 shown here

  1. pmc Structural basis for the differential effects of CaBP1 and calmodulin on Ca(V)1.2 calcium-dependent inactivation
    Felix Findeisen
    Cardiovascular Research Institute, University of California, San Francisco, CA 94158 2330, USA
    Structure 18:1617-31. 2010
    ..Discovery of this division provides the framework for understanding how CaBP1 regulates Ca(V)s...
  2. ncbi Molecular mechanism for divergent regulation of Cav1.2 Ca2+ channels by calmodulin and Ca2+-binding protein-1
    Hong Zhou
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 280:29612-9. 2005
    ..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...
  3. doi Hallmarks of the channelopathies associated with L-type calcium channels: a focus on the Timothy mutations in Ca(v)1.2 channels
    Isabelle Bidaud
    CNRS, UMR 5203, Institut de Genomique Fonctionnelle, Montpellier, France
    Biochimie 93:2080-6. 2011
    ..Among them, the Timothy syndrome (TS) is linked to missense mutations in CACNA1C, the gene that encodes the Ca(v)1.2 subunit. Here we review the important features of the Cav1 channelopathies...
  4. ncbi Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with Cav1.2 (L-type) Ca2+ channels
    Hong Zhou
    Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Neurosci 24:4698-708. 2004
    ..2 with these same voltage protocols. Our findings reveal how Ca2+-binding proteins, such as CaM and CaBP1, differentially adjust Ca2+ influx through Ca(v)1.2 channels, which may specify diverse modes of Ca2+ signaling in neurons...
  5. ncbi alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive calcium regulation
    Greg L Lyford
    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA
    Am J Physiol Cell Physiol 283:C1001-8. 2002
    ..These data demonstrate mechanical regulation of calcium entry through molecularly identified L-type calcium channels in mammalian cells and suggest that the mechanosensitivity resides within the pore forming alpha(1C)-subunit...
  6. doi Mapping of dihydropyridine binding residues in a less sensitive invertebrate L-type calcium channel (LCa v 1)
    Adriano Senatore
    Department of Biology, University of Waterloo, Waterloo, Ontario, Canada
    Channels (Austin) 5:173-87. 2011
    ..2. Interestingly, the single N_3o18_Q mutation in LCa(v) 1 channels lowers DHP sensitivity even further and the triple mutation bearing enhanced isradipine sensitivity, still retains a reduced potency of agonist, (S)-Bay K8644...
  7. pmc Ca(v)1.2 splice variant with exon 9* is critical for regulation of cerebral artery diameter
    Matthew A Nystoriak
    Department of Pharmacology and Surgery, University of Vermont, College of Medicine, Burlington, VT 05405 0068, USA
    Am J Physiol Heart Circ Physiol 297:H1820-8. 2009
    ..We conclude that although cerebral artery myocytes express both alpha(1)C(9/9*/10) and alpha(1)C(9/10) VDCC splice variants, alpha(1)C(9/9*/10) is functionally dominant in the control of cerebral artery diameter...
  8. ncbi Normalization of current kinetics by interaction between the alpha 1 and beta subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel
    A E Lacerda
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030
    Nature 352:527-30. 1991
    ....
  9. pmc Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart
    D Schultz
    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267 0575
    Proc Natl Acad Sci U S A 90:6228-32. 1993
    ..The cloned alpha 1 subunit was expressed in Xenopus oocytes and single-channel analyses revealed native-like pharmacology and channel properties...
  10. ncbi Tissue-specific expression of two human Ca(v)1.2 isoforms under the control of distinct 5' flanking regulatory elements
    Li Pang
    Department of Medicine, Montreal Heart Institute, and University of Montreal, 5000 Belanger St East, Montreal, QC, Canada H1T 1C8
    FEBS Lett 546:349-54. 2003
    ..These data indicate specific expression patterns of two human Ca(v)1.2 isoforms under the control of distinct 5' flanking regulatory sequences...
  11. pmc Amino acid substitutions in the pore of the Ca(V)1.2 calcium channel reduce barium currents without affecting calcium currents
    Xianming Wang
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Biophys J 89:1731-43. 2005
    ..In summary, the physicochemical properties of the amino acid residues at positions 1144 and 1152 are crucial to the pore's ability to distinguish between multiple Ba(2+) ions and Ca(2+) ions...
  12. ncbi Ahnak is critical for cardiac Ca(V)1.2 calcium channel function and its beta-adrenergic regulation
    Hannelore Haase
    Max Delbrück Center for Molecular Medicine MDC, D 13092 Berlin, Germany
    FASEB J 19:1969-77. 2005
    ..This genetic ahnak variant might cause individual differences in I(CaL) regulation upon physiological challenges or therapeutic interventions...
  13. ncbi Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac Ca(v)1.2 calcium channel
    Jennifer L Fallon
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Structure 13:1881-6. 2005
    ..These findings suggest that this structure could represent the conformation that calmodulin assumes in CDF...
  14. pmc Calmodulin-dependent gating of Ca(v)1.2 calcium channels in the absence of Ca(v)beta subunits
    Arippa Ravindran
    National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    Proc Natl Acad Sci U S A 105:8154-9. 2008
    ..We suggest that CaM(ex) affects specific Ca(v)beta-free conformations of the channel that are not available to endogenous CaM...
  15. pmc The intracellular II-III loops of Cav1.2 and Cav1.3 uncouple L-type voltage-gated Ca2+ channels from glucagon-like peptide-1 potentiation of insulin secretion in INS-1 cells via displacement from lipid rafts
    Sarah Melissa P Jacobo
    Program in Biochemistry and Molecular Biology, Purdue University, West Lafayette, Indiana, USA
    J Pharmacol Exp Ther 330:283-93. 2009
    ..These findings suggest that the II-III interdomain loops of Ca(v)1.2, and possibly Ca(v)1.3, direct these channels to membrane microdomains in which the proteins that mediate potentiation of GSIS by GLP-1 and 8-Br-cAMP assemble...
  16. pmc Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain
    Filip Van Petegem
    Cardiovascular Research Institute, Department of Biochemistry and Biophysics, University of California San Francisco, 513 Parnassus Avenue, Box 0130, San Francisco, California 94143, USA
    Nature 429:671-5. 2004
    ..Together, these data suggest that Ca(V)betas influence Ca(V) gating by direct modulation of IS6 movement within the channel pore...
  17. ncbi Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels
    Yu hang Chen
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nature 429:675-80. 2004
    ..The presence of multiple protein-interacting modules in the beta-subunit opens a new dimension to its function as a multi-functional protein...
  18. ncbi Transcript scanning reveals novel and extensive splice variations in human l-type voltage-gated calcium channel, Cav1.2 alpha1 subunit
    Zhen Zhi Tang
    Department of Physiology, National University of Singapore, Singapore 117597
    J Biol Chem 279:44335-43. 2004
    ..This systematic portrait of splice variation furnishes a reference library for comprehending combinatorial arrangements of Cav1.2 splice exons, especially as they impact development, physiology, and disease...
  19. pmc Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations
    Igor Splawski
    Howard Hughes Medical Institute, Department of Cardiology, and Genomics Program and Division of Genetics, Children s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:8089-96; discussion 8086-8. 2005
    ..These data indicate that gain-of-function mutations of CaV1.2 exons 8 and 8A cause distinct forms of TS...
  20. ncbi International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels
    William A Catterall
    Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280, USA
    Pharmacol Rev 57:411-25. 2005
    ..This article presents the molecular relationships and physiological functions of these calcium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties...
  21. ncbi CACNA1C polymorphisms are associated with the efficacy of calcium channel blockers in the treatment of hypertension
    Troy Bremer
    Prediction Sciences, 9404 Genesee Ave, Suite 210, La Jolla, CA 92037, USA
    Pharmacogenomics 7:271-9. 2006
    ..of 62 single nucleotide polymorphisms (SNPs) in the calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C) gene were obtained for each subject from a blood sample...
  22. ncbi L-type calcium channel alpha-subunit and protein kinase inhibitors modulate Rem-mediated regulation of current
    Shawn M Crump
    Dept of Physiology, MS 508, Univ of Kentucky College of Medicine, 800 Rose St Lexington, KY 40536 0298, USA
    Am J Physiol Heart Circ Physiol 291:H1959-71. 2006
    ..We conclude that Rem is capable of regulating L-type current, that release of Rem block is modulated by cellular kinase pathways, and that the Ca(V)1.2 COOH terminus contributes to Rem-dependent channel inhibition...
  23. pmc The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels
    Curtis F Barrett
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305 5345, USA
    Proc Natl Acad Sci U S A 105:2157-62. 2008
    ..Thus, the TS mutation offers a unique perspective on mechanisms of inactivation as well as a promising starting point for exploring the underlying pathophysiology of autism...
  24. pmc Whole-genome association study of bipolar disorder
    P Sklar
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
    Mol Psychiatry 13:558-69. 2008
    ..indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene...
  25. pmc Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder
    Manuel A R Ferreira
    Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Nat Genet 40:1056-8. 2008
    ..1 x 10(-9)) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 x 10(-8), rs1006737)...
  26. ncbi Genetic polymorphisms of L-type calcium channel alpha1C and alpha1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers
    Kei Kamide
    Division of Hypertension and Nephrology, Research Institute, National Cardiovascular Center, Suita, Japan
    Circ J 73:732-40. 2009
    ..The response of blood pressure (BP) to L-type dihydropyridine calcium-channel blockers (dCCBs) differs among individuals...
  27. pmc Coupled and independent contributions of residues in IS6 and IIS6 to activation gating of CaV1.2
    Michaela Kudrnac
    Department of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A 1090 Wien, Austria
    J Biol Chem 284:12276-84. 2009
    ..8 +/- 1.4 mV). Mutant cycle analysis revealed energetic coupling between residues Ser-435 and Ile-781, whereas other paired mutations in segments IS6 and IIS6 had independent effects on activation gating...
  28. pmc The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia
    E K Green
    Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK
    Mol Psychiatry 15:1016-22. 2010
    ..Strong evidence (P=7.0 × 10(-7)) of association at the polymorphism rs1006737 (within CACNA1C, the gene encoding the α-1C subunit of the L-type voltage-gated calcium channel) with the risk of bipolar ..
  29. doi Effect of CACNA1C rs1006737 on neural correlates of verbal fluency in healthy individuals
    Axel Krug
    Department of Psychiatry, Philipps University Marburg, Rudolf Bultmann Str 8, 35039 Marburg, Germany
    Neuroimage 49:1831-6. 2010
    ..found the A allele of the variant rs1006737 in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene to be overrepresented in patients suffering from bipolar disorder, schizophrenia or major depression...
  30. doi CaV1.2 channelopathies: from arrhythmias to autism, bipolar disorder, and immunodeficiency
    Ping Liao
    National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore
    Pflugers Arch 460:353-9. 2010
    ..Here, we will discuss how alternative splicing modulates CaV1.2 channelopathy and the role of CaV1.2 channel in both excitable and non-excitable tissues...
  31. doi Brain function in carriers of a genome-wide supported bipolar disorder variant
    Susanne Erk
    Division of Medical Psychology, University of Bonn, Bonn, Germany
    Arch Gen Psychiatry 67:803-11. 2010
    ..through genome-wide association, of a single-nucleotide polymorphism (rs1006737) strongly associated with bipolar disorder within the CACNA1C gene, encoding the alpha subunit of the L-type voltage-dependent calcium channel Ca(v)1.2.
  32. pmc Genetic variation in CACNA1C affects brain circuitries related to mental illness
    Kristin L Bigos
    Genes, Cognition, and Psychosis Program, Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
    Arch Gen Psychiatry 67:939-45. 2010
    The CACNA1C gene (alpha-1C subunit of the L-type voltage-gated calcium channel) has been identified as a risk gene for bipolar disorder and schizophrenia, but the mechanism of association has not been explored.
  33. pmc Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned
    N R Wray
    Genetic Epidemiology, Molecular Epidemiology, Psychiatric Genetics and Queensland Statistical Genetics Laboratories, Queensland Institute of Medical Research, Brisbane, QLD, Australia
    Mol Psychiatry 17:36-48. 2012
    ..of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1...
  34. doi Effects of a CACNA1C genotype on attention networks in healthy individuals
    M Thimm
    Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany
    Psychol Med 41:1551-61. 2011
    ..found the A allele of the variant rs1006737 in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene to be over-represented in patients with psychosis, including schizophrenia, bipolar disorder and major ..
  35. doi Initial evidence for the role of CACNA1C on subcortical brain morphology in patients with bipolar disorder
    E Perrier
    Medizinische Fakultat, Universitat zu Koln, Germany
    Eur Psychiatry 26:135-7. 2011
    The polymorphism rs1006737 within the CACNA1C gene is associated with increased risk for bipolar disorder (BD) and variations in brain morphology and function of subcortical regions...
  36. pmc Robust L-type calcium current expression following heterozygous knockout of the Cav1.2 gene in adult mouse heart
    Barbara Rosati
    Department of Physiology and Biophysics, BST Room 124, Level 6, Stony Brook University, Stony Brook, NY 11794 8661, USA
    J Physiol 589:3275-88. 2011
    ..The results are consistent with a model of L-type calcium channel biosynthesis in which there are one or more saturated steps, which act to buffer changes in both total Cav1.2 protein and L-type current expression...
  37. doi The CACNA1C and ANK3 risk alleles impact on affective personality traits and startle reactivity but not on cognition or gating in healthy males
    Panos Roussos
    Department of Psychiatry and Behavioral Sciences, University of Crete, Heraklion, Greece
    Bipolar Disord 13:250-9. 2011
    The rs10994336 ANK3 and rs1006737 CACNA1C genetic variants have recently been identified as the most consistent, genome-wide significant risk factors for bipolar disorder, while the CACNA1C variant has also been associated with ..
  38. pmc Timothy mutation disrupts the link between activation and inactivation in Ca(V)1.2 protein
    Katrin Depil
    Department of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A 1090 Vienna, Austria
    J Biol Chem 286:31557-64. 2011
    ..2 in the closed state. Such a structural hypothesis is supported by changes in activation gating induced by mutations of the G/A/G/A residues. The structural implications for Ca(V)1.2 activation and inactivation gating are discussed...
  39. doi ANK3, CACNA1C and ZNF804A gene variants in bipolar disorders and psychosis subphenotype
    Tristram A P Lett
    Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada
    World J Biol Psychiatry 12:392-7. 2011
    OBJECTIVES. The ANK3, CACNA1C and ZNF804A genes have been implicated in both bipolar disorders (BPD) and schizophrenia (SCZ)...
  40. pmc The effects of CACNA1C gene polymorphism on spatial working memory in both healthy controls and patients with schizophrenia or bipolar disorder
    Qiumei Zhang
    School of Mental Health, Jining Medical University, Jining, China
    Neuropsychopharmacology 37:677-84. 2012
    b>CACNA1C gene polymorphism (rs1006737) is a susceptibility factor for both schizophrenia (SCZ) and bipolar disorder (BP). However, its role in working memory, a cognitive function that is impaired in both diseases, is not clear...
  41. doi ANK3 and CACNA1C--missing genetic link for bipolar disorder and major depressive disorder in two German case-control samples
    Stefan Kloiber
    Max Planck Institute of Psychiatry, Kraepelinstrasse 2 10, Munich, Germany
    J Psychiatr Res 46:973-9. 2012
    ..genome-wide association studies (GWAS) and metaanalyses revealed genetic associations for ANK3 (ankyrin 3) and CACNA1C (alpha 1C subunit of the L-type voltage gated calcium channel) with bipolar disorder (BPD)...
  42. pmc CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease
    Shambhu Bhat
    Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
    Prog Neurobiol 99:1-14. 2012
    ..consistent genetic findings to have emerged from bipolar disorder genome wide association studies (GWAS) is with CACNA1C, a gene that codes for the α(1C) subunit of the Ca(v)1.2 voltage-dependent L-type calcium channel (LTCC)...
  43. pmc Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long QT syndrome
    Nicole J Boczek
    Center for Translational Science Activities, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, USA
    Circ Cardiovasc Genet 6:279-89. 2013
    ..Long QT syndrome (LQTS) is the most common cardiac channelopathy with 15 elucidated LQTS-susceptibility genes. Approximately 20% of LQTS cases remain genetically elusive...
  44. pmc Molecular diversity of L-type Ca2+ channel transcripts in human fibroblasts
    N M Soldatov
    Laboratory of Cell Biology, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021 6399
    Proc Natl Acad Sci U S A 89:4628-32. 1992
    ..The fourth diversity region is located at the C-terminal region and comprises insertions and deletions. It is suggested that these variations may give rise to multiple subforms of HFCC with altered electrophysiological properties...
  45. ncbi Genomic structure of human L-type Ca2+ channel
    N M Soldatov
    Laboratory of Cell Biology, Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021 6399
    Genomics 22:77-87. 1994
    ..The cDNA for the human fibroblast Ca2+ channel (CACNL1A1) was previously characterized...
  46. ncbi A potential site of functional modulation by protein kinase A in the cardiac Ca2+ channel alpha 1C subunit
    T Perets
    Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
    FEBS Lett 384:189-92. 1996
    ..This effect was independent of the presence of the beta subunit. Phosphorylation of serine 1928 of alpha 1C may mediate the modulatory effect of PKA on the cardiac voltage-dependent ca2+ channel...
  47. ncbi Ca2+ channel sensitivity towards the blocker isradipine is affected by alternative splicing of the human alpha1C subunit gene
    R D Zühlke
    Department of Pharmacology, University of Bern, Switzerland
    FEBS Lett 427:220-4. 1998
    ..Among seven alpha1C channels we observed up to 10-fold differences in IC50 values for isradipine, as well as changes in the voltage dependence of DHP action...
  48. ncbi Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism
    Igor Splawski
    Department of Cardiology, Children s Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA
    Cell 119:19-31. 2004
    ..These discoveries establish the importance of Ca(V)1.2 in human physiology and development and implicate Ca(2+) signaling in autism...
  49. ncbi Differential role of the alpha1C subunit tails in regulation of the Cav1.2 channel by membrane potential, beta subunits, and Ca2+ ions
    Evgeny Kobrinsky
    Laboratory of Clinical Investigation, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Biol Chem 280:12474-85. 2005
    ..Thus, cross-talk between the alpha1C C and N termini, beta subunit, and the cytoplasmic pore region confers the multifactorial regulation of Ca(v)1.2 channels...
  50. pmc Structural determinants of L-type channel activation in segment IIS6 revealed by a retinal disorder
    Annette Hohaus
    Institute for Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A 1090 Wien
    J Biol Chem 280:38471-7. 2005
    ..2. These four residues are completely conserved in high voltage-activated calcium channels suggesting that these channels may share a common mechanism of gating...
  51. doi Conditional forebrain deletion of the L-type calcium channel Ca V 1.2 disrupts remote spatial memories in mice
    Jessica A White
    Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan 48109 0069, USA
    Learn Mem 15:1-5. 2008
    ..2(cKO) mice exhibited significant impairments in spatial memory when examined 30 d after training, suggesting that Ca(V)1.2 plays a critical role in consolidation of remote spatial memories...
  52. pmc Molecular dynamics and mutational analysis of a channelopathy mutation in the IIS6 helix of Ca V 1.2
    Anna Stary
    Institute for Theoretical Chemistry, University of Vienna, Vienna, Austria
    Channels (Austin) 2:216-23. 2008
    ..2 gating. Our study illustrates that effects of mutations in the lower part of IIS6 may not be localized to the residue or even segment being mutated, but may affect conformations of interacting segments...
  53. doi Phenotypic effects of a bipolar liability gene among individuals with major depressive disorder
    Francesco Casamassima
    Division of Psychiatry, University of Pisa, Pisa, Italy
    Am J Med Genet B Neuropsychiatr Genet 153:303-9. 2010
    Variations in voltage-dependent calcium channel L-type, alpha 1C subunit (CACNA1C) gene have been associated with bipolar disorder in a recent meta-analysis of genome-wide association studies [Ferreira et al., 2008]...
  54. pmc Different pathways for activation and deactivation in CaV1.2: a minimal gating model
    Stanislav Beyl
    Department of Pharmacology and Toxicology, University of Vienna, 1090 Vienna, Austria
    J Gen Physiol 134:231-41; S1-2. 2009
    ..We speculate that structural changes induced by a proline substitution in this position may disturb the voltage-sensing domain...
  55. doi Genetic variation in CACNA1C, a gene associated with bipolar disorder, influences brainstem rather than gray matter volume in healthy individuals
    Barbara Franke
    Department of Human Genetics, Institute for Genetic and Metabolic Disorders, Center for Neuroscience, Radboud University Nijmegen Medical Center, The Netherlands
    Biol Psychiatry 68:586-8. 2010
    Genetic variation in CACNA1C has been repeatedly shown to increase risk for psychiatric disorders, with the strongest evidence for involvement in bipolar disorder...
  56. pmc Physicochemical properties of pore residues predict activation gating of Ca V1.2: a correlation mutation analysis
    Stanislav Beyl
    Institute for Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, Vienna, Austria
    Pflugers Arch 461:53-63. 2011
    ..The identified physicochemical properties in the analysed gating-sensitive positions (accessible surface area, side-chain flexibility, and hydrophobicity) predict the shifts of the activation curves of Ca(V)1.2...
  57. pmc The association of genetic variation in CACNA1C with structure and function of a frontotemporal system
    Fei Wang
    Department of Psychiatry, Yale School of Medicine, New Haven, CT 06511, USA
    Bipolar Disord 13:696-700. 2011
    A single nucleotide polymorphism at the CACNA1C gene (rs1006737) has been reported in genome-wide association studies to be associated with bipolar disorder (BD) with genome-wide significance...
  58. ncbi A new promoter for alpha1C subunit of human L-type cardiac calcium channel Ca(V)1.2
    Bosong Dai
    Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, TX 77555 0641, USA
    Biochem Biophys Res Commun 296:429-33. 2002
    ..The putative promoter exhibits 69% homology to its rat counterpart and displays functional promoter activity when transfected into heart cells in culture in luciferase-expressing constructs...
  59. ncbi Tissue distribution of a human Ca v 1.2 alpha1 subunit splice variant with a 75 bp insertion
    Eva M Graf
    Institut fur Pharmakologie und Toxikologie, Medizinische Fakultät Carl Gustav Carus der TU Dresden, Fetscherstr 74, D 01307 Dresden, Germany
    Cell Calcium 38:11-21. 2005
    ..We conclude that the +9* variant is present in all human tissues investigated so far, and suggest that expression in human atrium is associated with vascular smooth muscle and/or connective tissue cells...
  60. pmc Augmented behavioral response and enhanced synaptosomal calcium transport induced by repeated cocaine administration are decreased by calcium channel blockers
    K Mills
    Department of Pharmacology, Meharry Medical College, Nashville, TN 37208, USA
    Life Sci 81:600-8. 2007
    ..Flunarizine and diltiazem attenuated the behavioral response by decreasing calcium uptake and decreasing neurochemical release...
  61. doi L-type calcium channels and psychiatric disorders: A brief review
    Francesco Casamassima
    Division of Psychiatry, University of Pisa, Pisa, Italy
    Am J Med Genet B Neuropsychiatr Genet 153:1373-90. 2010
    ..the association of polymorphisms in the alpha 1C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with bipolar disorder...
  62. ncbi Gating of the HypoPP-1 mutations: II. Effects of a calcium-channel agonist BayK 8644
    Alexey Kuzmenkin
    Department of Applied Physiology, University of Ulm, 89069 Ulm, Germany
    Pflugers Arch 454:605-14. 2007
    ....
  63. ncbi The structures of the human calcium channel alpha 1 subunit (CACNL1A2) and beta subunit (CACNLB3) genes
    Y Yamada
    Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine, Japan
    Genomics 27:312-9. 1995
    ..by introns are well conserved between the CACNL1A2 gene and the previously reported L-type VDCC alpha 1 subunit, CACNL1A1, gene...
  64. pmc Multiple loops of the dihydropyridine receptor pore subunit are required for full-scale excitation-contraction coupling in skeletal muscle
    Leah Carbonneau
    Department of Physiology, University of Wisconsin School of Medicine, Madison, Wisconsin 53706, USA
    Biophys J 89:243-55. 2005
    ..Thus, despite the importance of the II-III loop there may be other critical determinants in alpha1S that influence the efficiency of EC coupling...
  65. ncbi Differential splicing patterns of L-type calcium channel Cav1.2 subunit in hearts of Spontaneously Hypertensive Rats and Wistar Kyoto Rats
    Zhen Zhi Tang
    Department of Physiology, National University of Singapore, Singapore 117597
    Biochim Biophys Acta 1783:118-30. 2008
    ..2 transcripts identified in SHR hearts provide a different and new perspective in understanding the possible role of molecular remodeling of Cav1.2 channels in cardiac hypertrophy as a consequence of hypertension...
  66. ncbi [Altered expression of L-type calcium channel alpha1C and alpha1D subunits in colon of rats with diarrhea-predominant irritable bowel syndrome]
    Jie Zhu
    Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China
    Zhonghua Yi Xue Za Zhi 89:2713-7. 2009
    ..To investigate the molecular identities of L-type calcium channel alpha1C subunit (Cav1.2) and alpha1D subunit (Cav1.3) responsible for motor dysfunction of diarrhea-predominant irritable bowel syndrome (D-IBS)...
  67. ncbi Insulin-like growth factor-1 increases skeletal muscle dihydropyridine receptor alpha 1S transcriptional activity by acting on the cAMP-response element-binding protein element of the promoter region
    Zhenlin Zheng
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Biol Chem 277:50535-42. 2002
    ..These results support the conclusion that IGF-1 regulates DHPR alpha(1S) transcription in muscle cells by acting on the CREB element of the promoter...
  68. ncbi Cardiac L-type calcium channel beta-subunits expressed in human heart have differential effects on single channel characteristics
    Roger Hullin
    Cardiology, Swiss Cardiovascular Heart Center Bern, University Hospital, 3010 Bern, Switzerland
    J Biol Chem 278:21623-30. 2003
    ..Moreover, differences in the various beta-subunit gene products present in human heart might account for altered single channel behavior found in human heart failure...
  69. pmc Differential modulation of L-type calcium channel subunits by oleate
    Yingrao Tian
    Department of Pharmacology and Toxicology, Virginia Commonwealth University Medical Center, Richmond, VA, USA
    Am J Physiol Endocrinol Metab 294:E1178-86. 2008
    ..3 and Cav1.2) appear to be targeted by nonesterified fatty acids. This effect may account in part for the acute potentiation of glucose-dependent insulin secretion by fatty acids...
  70. pmc CaMKII associates with CaV1.2 L-type calcium channels via selected beta subunits to enhance regulatory phosphorylation
    Sunday A Abiria
    Brain Institute, Vanderbilt University, Nashville, Tennessee, USA
    J Neurochem 112:150-61. 2010
    ..2alpha(1) and beta subunits. These findings demonstrate a biochemical mechanism underlying LTCC facilitation by CaMKII...
  71. ncbi L-type calcium channels in adrenal chromaffin cells: role in pace-making and secretion
    A Marcantoni
    Department of Neuroscience, NIS Center of Excellence, CNISM Research Unit, Corso Raffaello 30, 10125 Torino, Italy
    Cell Calcium 42:397-408. 2007
    ..Here we will review all these novel findings and discuss the possible implication for a specific role of L-type channels in the control of chromaffin cells activity...
  72. pmc Diversity and developmental expression of L-type calcium channel beta2 proteins and their influence on calcium current in murine heart
    Sabine Link
    Experimentelle und Klinische Pharmakologie und Toxikologie, Universitat des Saarlandes, 66421 Homburg, Germany
    J Biol Chem 284:30129-37. 2009
    ....
  73. pmc Amyloid precursor protein regulates Cav1.2 L-type calcium channel levels and function to influence GABAergic short-term plasticity
    Li Yang
    Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA
    J Neurosci 29:15660-8. 2009
    ..2. These results provide a direct link between APP and calcium signaling and might help explain how altered APP regulation leads to changes in synaptic function that occur with AD...
  74. ncbi GABAA receptor-mediated activation of L-type calcium channels induces neuronal excitation in surgically resected human hypothalamic hamartomas
    Do Young Kim
    Division of Pediatric Neurology, Barrow Neurological Institute, St Joseph s Hospital and Medical Center, Phoenix, AZ 85013, USA
    Epilepsia 49:861-71. 2008
    ..Here, we examined the role of GABAA receptors in surgically resected HH tissue...
  75. pmc A common single nucleotide polymorphism can exacerbate long-QT type 2 syndrome leading to sudden infant death
    Eyal Nof
    Masonic Medical Research Laboratory, Utica, NY 13501, USA
    Circ Cardiovasc Genet 3:199-206. 2010
    ..We present a family in which a common polymorphism (single nucleotide polymorphism) inherited from the father, combined with a stop codon mutation inherited from the mother (both asymptomatic), led to 2 cases of sudden infant death...
  76. ncbi Role of the synprint site in presynaptic targeting of the calcium channel CaV2.2 in hippocampal neurons
    Zsolt Szabo
    Department of Physiology and Medical Physics, Innsbruck Medical University, Fritz Pregl Str 3, A 6020 Innsbruck, Austria
    Eur J Neurosci 24:709-18. 2006
    ..The unique targeting properties of the splice variants lacking the synprint site are suggestive of specific functions of these calcium channels apart from activating fast synaptic transmission...
  77. pmc Src family tyrosine kinases mediate contraction of rat isolated tail arteries in response to a hyposmotic stimulus
    Sumangali Wijetunge
    Clinical Pharmacology, NHLI Division, Faculty of Medicine, Imperial College London, London, UK
    J Hypertens 25:1871-8. 2007
    ..2). We studied possible roles of tyrosine kinases, particularly src family kinases (SFK) and extracellular signal-related kinases (ERK1/2), in this response...
  78. doi A genome-wide linkage study of bipolar disorder and co-morbid migraine: replication of migraine linkage on chromosome 4q24, and suggestion of an overlapping susceptibility region for both disorders on chromosome 20p11
    K J Oedegaard
    Department of Psychiatry, University of California San Diego, La Jolla, CA 92093 0603, USA
    J Affect Disord 122:14-26. 2010
    ..regions of linkage on chromosomes, and two functionally similar voltage-dependent calcium channels CACNA1A and CACNA1C have been identified in familial hemiplegic migraine and recently implicated in two whole genome BPAD association ..
  79. ncbi Effects of extracellular pH on neuronal calcium channel activation
    C J Doering
    Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1
    Neuroscience 146:1032-43. 2007
    ....
  80. ncbi Antihypertensive effects of the putative T-type calcium channel antagonist mibefradil are mediated by the L-type calcium channel Cav1.2
    Sven Moosmang
    Institut fur Pharmakologie und Toxikologie, Technische Universitat Munchen, Germany
    Circ Res 98:105-10. 2006
    ..2SMAKO mice. These results demonstrate that the effect of the putative T-type Ca2+ channel-selective blocker mibefradil on blood pressure and small vessel myogenic tone is mediated by the Cav1.2 L-type Ca2+ channel...
  81. ncbi Altered localization of Cav1.2 (L-type) calcium channels in nerve fibers, Schwann cells, odontoblasts, and fibroblasts of tooth pulp after tooth injury
    R E Westenbroek
    Department of Pharmacology, University of Washington, Seattle, USA
    J Neurosci Res 75:371-83. 2004
    ..These findings provide new insight into the localization of Cav1.2 channels in dental pulp and sensory fibers, and demonstrate unexpected plasticity of channel distribution in response to nerve injury...
  82. ncbi Suramin interacts with the calmodulin binding site on the ryanodine receptor, RYR1
    Rao V L Papineni
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 277:49167-74. 2002
    ....
  83. ncbi The C2A domain of synaptotagmin alters the kinetics of voltage-gated Ca2+ channels Ca(v)1.2 (Lc-type) and Ca(v)2.3 (R-type)
    Roy Cohen
    Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    J Biol Chem 278:9258-66. 2003
    ..It indicates that calcium-independent properties of Syt 1 regulate voltage-gated Ca2+ channels and contribute to the molecular events underlying transmitter release...
  84. pmc Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart
    Nathalie Gaborit
    INSERM U533, Nantes, France
    J Physiol 582:675-93. 2007
    ..Concordance with previous functional studies suggests that regional regulation of cardiac ion-current expression may be primarily transcriptional...
  85. pmc Ablation of triadin causes loss of cardiac Ca2+ release units, impaired excitation-contraction coupling, and cardiac arrhythmias
    Nagesh Chopra
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 106:7636-41. 2009
    ....
  86. doi Phosphate and calcium are required for TGFbeta-mediated stimulation of ANK expression and function during chondrogenesis
    Paulina Oca
    Center for Translational Medicine, Department Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Cell Physiol 224:540-8. 2010
    ..Our findings indicate that TGFbeta stimulation of ANK expression is dependent upon the influx of phosphate and calcium into ATDC5 cells at all stages of differentiation...
  87. pmc Regulation of the mutually exclusive exons 8a and 8 in the CaV1.2 calcium channel transcript by polypyrimidine tract-binding protein
    Zhen Zhi Tang
    Howard Hughes Medical Institute, UCLA, Los Angeles, California 90095, USA
    J Biol Chem 286:10007-16. 2011
    ..The nPTB protein is a weaker repressor of exon 8a, resulting in a shift in exon choice when nPTB replaces PTB in cells. These results provide mechanistic understanding of how these two exons, important for human disease, are controlled...
  88. ncbi PKCdelta mediates testosterone-induced increases in coronary smooth muscle Cav1.2
    Kamala K Maddali
    Department of Biomedical Sciences, Dalton Cardiovascular Research Center, National Center for Gender Physiology, University of Missouri, Columbia, Missouri 65211, USA
    J Biol Chem 280:43024-9. 2005
    ..These results demonstrate for the first time that 1) endogenous T is a primary modulator of coronary PKCdelta protein and activity in males and 2) T increases Cav1.2 protein expression in a PKCdelta-dependent manner...
  89. doi Loss of Cav1.3 channels reveals the critical role of L-type and BK channel coupling in pacemaking mouse adrenal chromaffin cells
    Andrea Marcantoni
    Department of Neuroscience, Nanostructured Interfaces and Surfaces Centre of Excellence, Consorzio Nazionale Interuniversitario per le Scienze Fisiche della Materia, 10125 Torino, Italy
    J Neurosci 30:491-504. 2010
    ..2, as subthreshold pacemaker channels in MCCs and open new interesting features about their role in the control of firing and catecholamine secretion at rest and during sustained stimulations matching acute stress...
  90. pmc Potential relevance of alpha(1)-adrenergic receptor autoantibodies in refractory hypertension
    Katrin Wenzel
    Medical Faculty of the Charite, Franz Volhard Clinic and HELIOS Klinikum Berlin, Experimental and Clinical Research Center, Berlin, Germany
    PLoS ONE 3:e3742. 2008
    ..We implied earlier that alpha(1)-AAB might have a mechanistic role and could represent a therapeutic target...
  91. doi Funny current downregulation and sinus node dysfunction associated with atrial tachyarrhythmia: a molecular basis for tachycardia-bradycardia syndrome
    Yung Hsin Yeh
    Department of Medicine, Montreal Heart Institute Research Center and Université de Montréal, Montreal, Quebec, Canada
    Circulation 119:1576-85. 2009
    ..This study examined the hypothesis that ATs impair SAN function by altering ion channel expression...
  92. pmc The genetics of bipolar disorder
    J H Barnett
    Center for Human Genetic Research, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA
    Neuroscience 164:331-43. 2009
    ..genes for a variety of complex disorders, has begun to implicate specific genes for bipolar disorder (DGKH, CACNA1C, ANK3)...
  93. ncbi Expression of recombinant calcium channels support secretion in a mouse pheochromocytoma cell line
    Amy B Harkins
    Department of Neurobiology, Pharmacology, and Physiology, The University of Chicago, Chicago, Illinois 60637, USA
    J Neurophysiol 90:2325-33. 2003
    ..This model may help to distinguish the roles that different Ca2+ channels play in Ca2+-dependent secretion...
  94. ncbi Cav1.2 calcium channels modulate the spiking pattern of hippocampal pyramidal cells
    Lubica Lacinova
    Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska 5, 833 34 Bratislava, Slovakia
    Life Sci 82:41-9. 2008
    ..2 channels are involved in regulating the intrinsic excitability of CA1 pyramidal neurons. This cellular mechanism may contribute to the known function of Ca(v)1.2 channels in supporting synaptic plasticity and memory...
  95. pmc Congenital long QT syndrome
    Lia Crotti
    Section of Cardiology, Department of Lung, Blood and Heart, University of Pavia, Pavia, Italy
    Orphanet J Rare Dis 3:18. 2008
    ..Mutations in these genes (KCNQ1, KCNH2, KCNE1, KCNE2, CACNA1c, CAV3, SCN5A, SCN4B) cause the disease by prolonging the duration of the action potential...
  96. pmc Accelerated inactivation of the L-type calcium current due to a mutation in CACNB2b underlies Brugada syndrome
    Jonathan M Cordeiro
    Department of Experimental Cardiology, Masonic Medical Research Laboratory, Utica, NY 13501, USA
    J Mol Cell Cardiol 46:695-703. 2009
    Recent studies have demonstrated an association between mutations in CACNA1c or CACNB2b and Brugada syndrome (BrS). Previously described mutations all caused a loss of function secondary to a reduction of peak calcium current (I(Ca))...
  97. pmc Cell Cycle-Dependent Localization of Voltage-Dependent Calcium Channels and the Mitotic Apparatus in a Neuroendocrine Cell Line(AtT-20)
    Karen J Loechner
    Division of Pediatric Endocrinology, Department of Pediatrics, University of North Carolina Chapel Hill, Chapel Hill, NC 27599, USA
    Int J Cell Biol 2009:487959. 2009
    ....
  98. ncbi Enhancement of cardiac L-type Ca2+ currents in transgenic mice with cardiac-specific overexpression of CYP2J2
    Yong Fu Xiao
    Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
    Mol Pharmacol 66:1607-16. 2004
    ..In conclusion, overexpression of CYP2J2 increases ICa in CYP2J2 transgenic cardiomyocytes via a mechanism that involves cAMP-protein kinase A-dependent phosphorylation of the L-type Ca2+ channel...

Research Grants65

  1. Functional Studies of Variants of the Bipolar Risk Gene CACNA1C in Human Neurons
    JEN PAN; Fiscal Year: 2013
    ..Calcium ion channels are important drug targets for hypertension and neuropathic pain. Coding mutations in the CACNA1C calcium ion channel gene cause a rare hereditary disorder called Timothy Syndrome, affecting the heart, the brain,..
  2. Gonadal Hormones and Depression:The Role of Mood Disorder Risk Gene CACNA1C
    Todd D Gould; Fiscal Year: 2012
    ..Numerous recent human genetic studies indicate a robust association between polymorphisms in CACNA1C, a gene that codes for the 11 subunit of the CaV1...
  3. Neuronal-Specific Splicing of CaV1.2 L-type Calcium Channels
    Kristin Webster; Fiscal Year: 2013
    ..I hypothesize that the e1b isoform will more efficiently induce CREB phosphorylation. These experiments will advance our understanding of how neuronal specific isoforms of CaV1.2 contribute to essential neuronal functions. ..
  4. Chemokine receptor-4 regulation of Beta adrenergic-mediated calcium channel
    Sima T Tarzami; Fiscal Year: 2012
    ....
  5. SHAWN BRADY BENDER; Fiscal Year: 2016
    ..IR will be induced in wild-type and VSMC MR KO mice with a high-fat, high-sucrose diet and will be assessed by glucose tolerance testing. ..
  6. Single nucleotide polymorphisms of neuronal CACNA1C L-type calcium channels assoc
    Diane Lipscombe; Fiscal Year: 2011
    ..Calcium ion channels are important drug targets for treating hypertension and neuropathic pain. Mutations in the CACNA1C calcium ion channel gene cause a rare hereditary disorder Timothy Syndrome and single nucleotide polymorphisms ..
  7. Chronic stress-induced gene expression in colonic circular smooth muscle cells.
    Sushil K Sarna; Fiscal Year: 2012
    ..The findings of this proposal are expected to identify the potential molecular therapeutic approaches that may prevent or minimize the ill effects of chronic stress on colonic motility function. ..
  8. AKAP Regulation of Neuronal L-type Calcium Channel Signaling to the Nucleus
    MARK L DELL'ACQUA; Fiscal Year: 2013
    ....
  9. Regulation of Cardiac Gene Expression by the L-type Calcium Channel, CaV1.2.
    ROBERT NATHAN CORRELL; Fiscal Year: 2011
    ..This work will help reveal the role of the cardiac L-type Ca2+ channel in regulation of gene expression related to disease and may suggest new translational strategies to combat heart failure. ..
  10. Secretagogue induced mechanisms regulating islet electrical activity
    DAVID AARON JACOBSON; Fiscal Year: 2012
    ..Understanding how secretagogues regulate islet electrical activity distinctly from KATP may help to develop new therapies that target specific elements of the excitation-secretion pathway. ..
  11. L-type Ca2+ Channel Modulation of Beta Cell Function
    GREGORY HOWARD HOCKERMAN; Fiscal Year: 2012
    ..This proposal is consistent with the PI's long term goal of understanding L-type calcium channel modulation and cellular function. ..
  12. Luis F Santana; Fiscal Year: 2016
    ..2 channel that causes arrhythmias and autism in humans with long QT syndrome 8 (LQT8)...
  13. Fibroblast Growth Factor Homologous Factors: Modulation of L-type Calcium Channel
    JESSICA AMENTA HENNESSEY; Fiscal Year: 2013
    ..This will demonstrate that FGF13 is a prominent player in the cardiac action potential through its modulation of the LTCC and define FGF13 dysfunction as a mediator of acquired and inherited arrhythmias. ..
  14. L-type Calcium Channel Regulation of Neuronal Differentiation
    Georgia Panagiotakos; Fiscal Year: 2012
    ..These studies will expand our understanding of how activity regulates brain development and will provide new insights into the underlying pathophysiology of autism and mental retardation. ..
  15. Masayuki Yazawa; Fiscal Year: 2015
    ..abstract_text> ..
  16. Model of Timothy Syndrome to Screen Drugs with Induced Pluripotent Stem Cells
    Masayuki Yazawa; Fiscal Year: 2013
    ..The proposed systems to screen a library of compounds to rescue TS phenotypes will provide a platform to find novel lead compounds that would be clinically useful for the treatment of not only TS but also other cardiac arrhythmias. ..
  17. The Role of Calcium Signaling in Stem Cell Quiescence
    Gozde Yucel; Fiscal Year: 2010
    ..Consistent with this finding, conditional ablation of CACNA1C (CaVI ...
  18. MicroRNA to decrease vascular CaV1.2 in hypertension
    Philip T Palade; Fiscal Year: 2013
    ..A longer lasting therapy with fewer side effects may be extremely beneficial for the >40 million Americans whose hypertension is not properly managed. ..
  19. Reciprocal Control of Ca2+ Channels by Anchored Protein Kinase A and Calcineurin
    William A Sather; Fiscal Year: 2010
    ..A mutation in the calcium channel studied here has been identified as the cause of Timothy syndrome in humans, symptoms of which are cognitive impairment and potentially fatal disturbance of heart rhythm. ..
  20. OLIVIA RUTH BUONARATI; Fiscal Year: 2015
    ..2-associated disorders in the central nervous system, including stroke, depression, anxiety, senility and Alzheimer's disease. ..
  21. 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. ..
  22. Calcium channels in arterial smooth muscle cells
    Jonathan H Jaggar; Fiscal Year: 2013
    ..2 channels are expressed in arterial smooth muscle cells, and that the molecular composition of these channels is altered in hypertension, leading to vasoconstriction. ..
  23. Regulation of Calcium Channel Function by the Rem GTPase
    Jonathan Satin; Fiscal Year: 2013
    ....
  24. PABLO MARTIN PAEZ; Fiscal Year: 2016
    ..These findings could lead to novel approaches to intervene in neurodegenerative diseases in which myelin is lost or damaged. ..
  25. Myocardial Properties of Timothy Syndrome
    RANDALL RASMUSSON; Fiscal Year: 2009
    ..Patients with Timothy Syndrome die at an average age of 2.5 years. In order to better understand and treat this disorder we will study a mouse in which the same genetic defect has been artificially introduced. ..
  26. Exploring the Neuronal Phenotype of Autism Spectrum Disorders Using Induced Pluri
    JOACHIM F contact HALLMAYER; Fiscal Year: 2010
    ..iPS cells from human fibroblasts harvested from healthy controls and ASD patients with mutations in the CACNA1C and SHANK3 gene, mutations known to affect neuronal development, and optimize and characterize the ..
  27. Central Synaptic Transmission in Drosophila.
    DIANE O DOWD; Fiscal Year: 2009
    ..Thus knowledge of the cellular mechanisms contributing to the behavioral deficits in cac mutant flies should also contribute to understanding of human diseases associated with mutant calcium channel genes. ..
  28. Cav1.2 Transcript Regulation in Heart and Smooth Muscle
    Philip Palade; Fiscal Year: 2007
    ..They could suggest new targets for pharmaceutical intervention in disorders involving alterations in expression of L-type Ca channels, such as hypertension. [unreadable] [unreadable] [unreadable]..
  29. Store operated calcium influx in cells of the immune system
    JEAN PIERRE M KINET; Fiscal Year: 2012
    ..2 (Aim 2) and CaV1.3 (Aim 3) interact and modulate CRAC channels. These studies will yield new insights into the molecular regulation of SOCE within T cells, enabling the development new approaches to treat autoimmune diseases. ..
  30. Exploring the Neuronal Phenotype of Autism Spectrum Disorders Using Induced Pluri
    Joachim F Hallmayer; Fiscal Year: 2013
    ..iPS cells from human fibroblasts harvested from healthy controls and ASD patients with mutations in the CACNA1C and SHANK3 gene, mutations known to affect neuronal development, and optimize and characterize the ..
  31. Regulation of Vascular Smooth Muscle Calcium by NADPH Redox
    Sachin A Gupte; Fiscal Year: 2012
    ..This study, on completion as anticipated, will prove to be useful in developing novel therapies for the treatment of vascular dysfunction in pulmonary hypertension, diabetes, and heart failure. Project Description Page 6 ..
  32. Abraham A Palmer; Fiscal Year: 2014
    ..We are focusing our efforts on the gene Cacna1c, which is among the most robust findings to emerge from genome-wide association studies (GWAS) of psychiatric ..
  33. Kirk W Evanson; Fiscal Year: 2014
    ..This research will reveal novel mechanisms of vascular contractility regulation by the CaV1.2 channel C-terminus. ..
  34. Ebenezer N Yamoah; Fiscal Year: 2014
    ..These studies should reveal how HCs and SGNs coordinate and regulate their electrical and biochemical machinery, information that might be exploited to induce HC and SGN survival after damage. ..
  35. Tingting Hong; Fiscal Year: 2015
    ..abstract_text> ..
  36. BIN1 is a mediator and marker of cardiac reserve in heart failure.
    Tingting Hong; Fiscal Year: 2013
    ....
  37. Kathleen D Keef; Fiscal Year: 2016
    ..Such information is critical for developing new strategies to help prevent as well as diagnose and treat IAS dysfunction. ..
  38. Geoffrey S Pitt; Fiscal Year: 2016
    ....
  39. Mechanisms of Ca2+ and voltage-dependent inactivation Ca channels
    MANU B JOHNY; Fiscal Year: 2013
    ..It would also provide a stepping stone to advance our understanding of the mechanistic consequences of lethal channelopathies raising hope for targeted therapeutic interventions. ..
  40. Sara K Quinney; Fiscal Year: 2016
    ..Pharmacogenetic variations in nifedipine pathway genes, e.g. CYP3A4, CYP3A5, CACNA1C, and CACN1C, will be tested for association with tocolytic response to nifedipine...
  41. Luis F Santana; Fiscal Year: 2016
    ..This work will generate fundamental information on the mechanisms by which AKAP150 and CaV1.2 channels control of excitability, gene expression, and EC coupling in vascular smooth muscle under physiological and pathological conditions. ..
  42. Ronghua Zhuge; Fiscal Year: 2016
    ..Such advances will deepen our understanding of ASM biology and facilitate the development of bitter tastants as new bronchodilators. ..
  43. ANNI SEUNGEUN LEE; Fiscal Year: 2015
    ..Since these analyses will be performed on behaviorally characterized mice, it will allow for association of molecular and behavioral consequences of prefrontal cortical Cav1.2 manipulations. ..
  44. Geoffrey S Pitt; Fiscal Year: 2016
    ..This proposal addresses how Ca2+ feeds back to regulate cardiac ion channels and examines the structure of critical domains in ion channels that are loci for inherited arrhythmogenic mutations. ..
  45. Johannes W Hell; Fiscal Year: 2016
    ..Because ? ARs also associate with Cav1.2 in heart, smooth muscle and pancreas, spatially restricted cAMP signaling is of wide interest beyond its role in the brain. ..
  46. Subcellular Localization of Cav1.2 by alpha-actinin
    Johannes W Hell; Fiscal Year: 2011
    ..2 surface expression and localization is regulated. It will thereby contribute to the development of treatment of these diseases. ..
  47. POSTSYNAPTIC SIGNALING PATHWAYS
    Johannes W Hell; Fiscal Year: 2010
    ..2 constitutes, therefore, a potentially effective and specific target for drugs that disrupt some of these interactions, thereby inhibiting adverse signaling events under pathological conditions. ..
  48. PROSPER N'GOUEMO; Fiscal Year: 2015
    ..PHS 398/2590 (Rev. 06/09) Page Continuation Format Page ..
  49. Anjali M Rajadhyaksha; Fiscal Year: 2016
    ..The results obtained from this study could greatly advance the field of cocaine addiction by identifying discrete molecular targets for developing pharmacological treatments for cocaine addicts. ..
  50. Nipavan Chiamvimonvat; Fiscal Year: 2016
    ..Indeed, novel insights into the atrial-specific and pacemaking tissue-specific ion channels may provide new means to target these channels without interfering with the excitability of ventricular tissues. ..
  51. Jason L Poulos; Fiscal Year: 2014
    ....
  52. Jin Peng Szatkiewicz; Fiscal Year: 2014
    ..identification of significant genome wide association for four genes which have confirmed miR-137 target sites (CACNA1C, TCF4, CSMD1, and C10orf26)...
  53. Modulation of Cav 1.3 L-type Ca2+ channels by PDZ-protein interactions
    Amy Lee; Fiscal Year: 2012
    ..We will elucidate new structure/function relationships and modulatory mechanisms, which may be altered in diseased states of the cardiovascular and nervous systems. ..
  54. Mechanisms of Long-term Cardiac Ion Channel Regulation
    Jonathan Satin; Fiscal Year: 2013
    ..We will determine the compensatory changes of SL Ca handling proteins in response to LTCC blockade. This work may provide a missing molecular link between LTCC function and downstream signaling events. ..
  55. MANU B JOHNY; Fiscal Year: 2016
    ..3) To deduce, using Aim 2 insight, the mechanism whereby RNA editing of CaV1.3 channels alters their CaM regulation. ..
  56. Development of High Throughput Assays for N-type Calcium Channels
    Edward Perez Reyes; Fiscal Year: 2007
    ..By targeting an important protein in the pain pathway, the research funded by this grant will provide tools that can be used to screen candidate compounds during the development of novel analgesics. [unreadable] [unreadable] [unreadable]..
  57. Central Synaptic Transmission in Drosophila.
    DIANE K O apos DOWD; Fiscal Year: 2010
    ....
  58. Calmodulin Domain Interactions with L-type Ca2+ Channels
    TURAN EVANS; Fiscal Year: 2007
    ..These studies will lead to a better understanding of the role of CaM domains in regulating conformational change in Cav1.2 which plays an essential role in regulating heartbeat. [unreadable] [unreadable] [unreadable]..
  59. Austin 5HT Candidate Gene Discovery with C Elegans
    J Jay Gargus; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  60. TRAINING IN MOLECULAR NEUROBIOLOGY
    William Catterall; Fiscal Year: 2008
    ..The training program will integrate the substantial expertise of this group of faculty in a coordinated pre-doctoral and post-doctoral training effort. ..
  61. SNP-based lithium treatment outcome diagnostic
    Troy Bremer; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  62. Mitochondrial regulation of calcium signaling
    JONATHAN JAGGAR; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  63. MOLECULAR MECHANISMS OF ARRHYTHMIAS DURING HEART FAILURE
    LUIS SANTANA; Fiscal Year: 2004
    ..The proposed work should provide fundamental information on the molecular mechanisms underlying arrhythmias during HF and could provide insights in the development of effective therapeutic strategies for this condition. ..
  64. Proton as co-transmitter of neuronal signaling
    Martin Morad; Fiscal Year: 2006
    ..abstract_text> ..
  65. Ion channel regulation by macromolecular complexes
    Steven O Marx; Fiscal Year: 2010
    ..Since heart failure and hypertrophy are associated with alterations in PKC activity and Ca2+ homeostasis, understanding the PKC modulation of Cav1.2 may contribute to the development of novel therapeutic agents to treat these disorders. ..