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
Products:     CACNA1C

Top Publications

  1. Thimm M, Kircher T, Kellermann T, Markov V, Krach S, Jansen A, et al. Effects of a CACNA1C genotype on attention networks in healthy individuals. Psychol Med. 2011;41:1551-61 pubmed publisher
    ..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 ..
  2. Nyegaard M, Demontis D, Foldager L, Hedemand A, Flint T, Sørensen K, et al. CACNA1C (rs1006737) is associated with schizophrenia. Mol Psychiatry. 2010;15:119-21 pubmed publisher
  3. Wang F, McIntosh A, He Y, Gelernter J, Blumberg H. The association of genetic variation in CACNA1C with structure and function of a frontotemporal system. Bipolar Disord. 2011;13:696-700 pubmed publisher
    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...
  4. Lett T, Zai C, Tiwari A, Shaikh S, Likhodi O, Kennedy J, et al. ANK3, CACNA1C and ZNF804A gene variants in bipolar disorders and psychosis subphenotype. World J Biol Psychiatry. 2011;12:392-7 pubmed publisher
    OBJECTIVES. The ANK3, CACNA1C and ZNF804A genes have been implicated in both bipolar disorders (BPD) and schizophrenia (SCZ)...
  5. Perrier E, Pompei F, Ruberto G, Vassos E, Collier D, Frangou S. Initial evidence for the role of CACNA1C on subcortical brain morphology in patients with bipolar disorder. Eur Psychiatry. 2011;26:135-7 pubmed publisher
    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...
  6. Beyl S, Kügler P, Kudrnac M, Hohaus A, Hering S, Timin E. Different pathways for activation and deactivation in CaV1.2: a minimal gating model. J Gen Physiol. 2009;134:231-41; S1-2 pubmed publisher
    ..We speculate that structural changes induced by a proline substitution in this position may disturb the voltage-sensing domain. ..
  7. Ferreira M, O Donovan M, Meng Y, Jones I, Ruderfer D, Jones L, et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet. 2008;40:1056-8 pubmed publisher
    ..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)...
  8. Kloiber S, Czamara D, Karbalai N, Muller Myhsok B, Hennings J, Holsboer F, et al. ANK3 and CACNA1C--missing genetic link for bipolar disorder and major depressive disorder in two German case-control samples. J Psychiatr Res. 2012;46:973-9 pubmed publisher
    ..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)...
  9. Zhang Q, Shen Q, Xu Z, Chen M, Cheng L, Zhai J, et al. The effects of CACNA1C gene polymorphism on spatial working memory in both healthy controls and patients with schizophrenia or bipolar disorder. Neuropsychopharmacology. 2012;37:677-84 pubmed publisher
    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...

More Information

Publications77

  1. Tang Z, Liang M, Lu S, Yu D, Yu C, Yue D, et al. Transcript scanning reveals novel and extensive splice variations in human l-type voltage-gated calcium channel, Cav1.2 alpha1 subunit. J Biol Chem. 2004;279:44335-43 pubmed
    ..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...
  2. Splawski I, Timothy K, Sharpe L, Decher N, Kumar P, Bloise R, et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004;119:19-31 pubmed
    ..These discoveries establish the importance of Ca(V)1.2 in human physiology and development and implicate Ca(2+) signaling in autism. ..
  3. Splawski I, Timothy K, Decher N, Kumar P, Sachse F, Beggs A, et al. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci U S A. 2005;102:8089-96; discussion 8086-8 pubmed
    ..These data indicate that gain-of-function mutations of CaV1.2 exons 8 and 8A cause distinct forms of TS. ..
  4. Green E, Grozeva D, Jones I, Jones L, Kirov G, Caesar S, et al. The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Mol Psychiatry. 2010;15:1016-22 pubmed publisher
    ..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 ..
  5. Stary A, Kudrnac M, Beyl S, Hohaus A, Timin E, Wolschann P, et al. Molecular dynamics and mutational analysis of a channelopathy mutation in the IIS6 helix of Ca V 1.2. Channels (Austin). 2008;2:216-23 pubmed
    ..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. ..
  6. Soldatov N. Genomic structure of human L-type Ca2+ channel. Genomics. 1994;22:77-87 pubmed
    ..The cDNA for the human fibroblast Ca2+ channel (CACNL1A1) was previously characterized...
  7. Casamassima F, Huang J, Fava M, Sachs G, Smoller J, Cassano G, et al. Phenotypic effects of a bipolar liability gene among individuals with major depressive disorder. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:303-9 pubmed publisher
    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]...
  8. Soldatov N. Molecular diversity of L-type Ca2+ channel transcripts in human fibroblasts. Proc Natl Acad Sci U S A. 1992;89:4628-32 pubmed
    ..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. ..
  9. Perets T, Blumenstein Y, Shistik E, Lotan I, Dascal N. A potential site of functional modulation by protein kinase A in the cardiac Ca2+ channel alpha 1C subunit. FEBS Lett. 1996;384:189-92 pubmed
    ..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. ..
  10. Sklar P, Smoller J, Fan J, Ferreira M, Perlis R, Chambert K, et al. Whole-genome association study of bipolar disorder. Mol Psychiatry. 2008;13:558-69 pubmed publisher
    ..indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene...
  11. Hohaus A, Beyl S, Kudrnac M, Berjukow S, Timin E, Marksteiner R, et al. Structural determinants of L-type channel activation in segment IIS6 revealed by a retinal disorder. J Biol Chem. 2005;280:38471-7 pubmed
    ..2. These four residues are completely conserved in high voltage-activated calcium channels suggesting that these channels may share a common mechanism of gating. ..
  12. Krug A, Nieratschker V, Markov V, Krach S, Jansen A, Zerres K, et al. Effect of CACNA1C rs1006737 on neural correlates of verbal fluency in healthy individuals. Neuroimage. 2010;49:1831-6 pubmed publisher
    ..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...
  13. Boczek N, Best J, Tester D, Giudicessi J, Middha S, Evans J, et al. Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long QT syndrome. Circ Cardiovasc Genet. 2013;6:279-89 pubmed
    ..Genomic triangulation combined with bioinformatic tools and ranking algorithms led to the identification of a CACNA1C mutation...
  14. Beyl S, Depil K, Hohaus A, Stary Weinzinger A, Timin E, Shabbir W, et al. Physicochemical properties of pore residues predict activation gating of Ca V1.2: a correlation mutation analysis. Pflugers Arch. 2011;461:53-63 pubmed publisher
    ..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. ..
  15. Bhat S, Dao D, Terrillion C, Arad M, Smith R, Soldatov N, et al. CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease. Prog Neurobiol. 2012;99:1-14 pubmed publisher
    ..consistent genetic findings to have emerged from bipolar disorder genome wide association studies (GWAS) is with CACNA1C, a gene that codes for the ?(1C) subunit of the Ca(v)1.2 voltage-dependent L-type calcium channel (LTCC)...
  16. Bigos K, Mattay V, Callicott J, Straub R, Vakkalanka R, Kolachana B, et al. Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch Gen Psychiatry. 2010;67:939-45 pubmed publisher
    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...
  17. Kudrnac M, Beyl S, Hohaus A, Stary A, Peterbauer T, Timin E, et al. Coupled and independent contributions of residues in IS6 and IIS6 to activation gating of CaV1.2. J Biol Chem. 2009;284:12276-84 pubmed publisher
    ..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. ..
  18. Erk S, Meyer Lindenberg A, Schnell K, Opitz von Boberfeld C, Esslinger C, Kirsch P, et al. Brain function in carriers of a genome-wide supported bipolar disorder variant. Arch Gen Psychiatry. 2010;67:803-11 pubmed publisher
    ..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...
  19. Kobrinsky E, Tiwari S, Maltsev V, Harry J, Lakatta E, Abernethy D, et al. Differential role of the alpha1C subunit tails in regulation of the Cav1.2 channel by membrane potential, beta subunits, and Ca2+ ions. J Biol Chem. 2005;280:12474-85 pubmed
    ..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. ..
  20. Chen Y, Li M, Zhang Y, He L, Yamada Y, Fitzmaurice A, et al. Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels. Nature. 2004;429:675-80 pubmed
    ..The presence of multiple protein-interacting modules in the beta-subunit opens a new dimension to its function as a multi-functional protein. ..
  21. Depil K, Beyl S, Stary Weinzinger A, Hohaus A, Timin E, Hering S. Timothy mutation disrupts the link between activation and inactivation in Ca(V)1.2 protein. J Biol Chem. 2011;286:31557-64 pubmed publisher
    ..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. ..
  22. . Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet. 2011;43:977-83 pubmed publisher
    ..11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4...
  23. Catterall W, Perez Reyes E, Snutch T, Striessnig J. International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev. 2005;57:411-25 pubmed
    ..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. ..
  24. Barrett C, Tsien R. The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. Proc Natl Acad Sci U S A. 2008;105:2157-62 pubmed publisher
    ..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. ..
  25. Liao P, Soong T. CaV1.2 channelopathies: from arrhythmias to autism, bipolar disorder, and immunodeficiency. Pflugers Arch. 2010;460:353-9 pubmed publisher
    ..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. ..
  26. Wray N, Pergadia M, Blackwood D, Penninx B, Gordon S, Nyholt D, et al. Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned. Mol Psychiatry. 2012;17:36-48 pubmed publisher
    ..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...
  27. White J, McKinney B, John M, Powers P, Kamp T, Murphy G. Conditional forebrain deletion of the L-type calcium channel Ca V 1.2 disrupts remote spatial memories in mice. Learn Mem. 2008;15:1-5 pubmed publisher
    ..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. ..
  28. Roussos P, Giakoumaki S, Georgakopoulos A, Robakis N, Bitsios P. The CACNA1C and ANK3 risk alleles impact on affective personality traits and startle reactivity but not on cognition or gating in healthy males. Bipolar Disord. 2011;13:250-9 pubmed publisher
    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 ..
  29. . Genome-wide association study identifies five new schizophrenia loci. Nat Genet. 2011;43:969-76 pubmed publisher
    ..disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7...
  30. Zühlke R, Bouron A, Soldatov N, Reuter H. Ca2+ channel sensitivity towards the blocker isradipine is affected by alternative splicing of the human alpha1C subunit gene. FEBS Lett. 1998;427:220-4 pubmed
    ..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. ..
  31. Rosati B, Yan Q, Lee M, Liou S, Ingalls B, Foell J, et al. Robust L-type calcium current expression following heterozygous knockout of the Cav1.2 gene in adult mouse heart. J Physiol. 2011;589:3275-88 pubmed publisher
    ..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. ..
  32. Van Petegem F, Clark K, Chatelain F, Minor D. Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain. Nature. 2004;429:671-5 pubmed
    ..Together, these data suggest that Ca(V)betas influence Ca(V) gating by direct modulation of IS6 movement within the channel pore. ..
  33. Kamide K, Yang J, Matayoshi T, Takiuchi S, Horio T, Yoshii M, et al. 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. Circ J. 2009;73:732-40 pubmed
    ..with dCCBs to study whether genetic polymorphisms of the calcium channel alpha1C and alpha1D subunit genes, CACNA1C and CACNA1D, are associated with the antihypertensive effects of dCCBs...
  34. Bremer T, Man A, Kask K, Diamond C. CACNA1C polymorphisms are associated with the efficacy of calcium channel blockers in the treatment of hypertension. Pharmacogenomics. 2006;7:271-9 pubmed
    ..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...
  35. Franke B, Vasquez A, Veltman J, Brunner H, Rijpkema M, Fernandez G. Genetic variation in CACNA1C, a gene associated with bipolar disorder, influences brainstem rather than gray matter volume in healthy individuals. Biol Psychiatry. 2010;68:586-8 pubmed publisher
    Genetic variation in CACNA1C has been repeatedly shown to increase risk for psychiatric disorders, with the strongest evidence for involvement in bipolar disorder...
  36. Crump S, Correll R, Schroder E, Lester W, Finlin B, Andres D, et al. L-type calcium channel alpha-subunit and protein kinase inhibitors modulate Rem-mediated regulation of current. Am J Physiol Heart Circ Physiol. 2006;291:H1959-71 pubmed
    ..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. ..
  37. Garcia Alvarez G, Shetty M, Lu B, Yap K, Oh Hora M, Sajikumar S, et al. Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes. Front Behav Neurosci. 2015;9:180 pubmed publisher
    ..Our findings also reveal an inverse correlation between LTP and spatial learning/memory and suggest that abnormal enhancement of cAMP/PKA signaling and synaptic efficacy disrupts the formation of new memories. ..
  38. Kabir Z, Martinez Rivera A, Rajadhyaksha A. From Gene to Behavior: L-Type Calcium Channel Mechanisms Underlying Neuropsychiatric Symptoms. Neurotherapeutics. 2017;14:588-613 pubmed publisher
    The L-type calcium channels (LTCCs) Cav1.2 and Cav1.3, encoded by the CACNA1C and CACNA1D genes, respectively, are important regulators of calcium influx into cells and are critical for normal brain development and ..
  39. Boczek N, Gómez Hurtado N, Ye D, Calvert M, Tester D, Kryshtal D, et al. Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome and Functional Characterization of a Novel Long QT Syndrome-Associated Calmodulin Missense Variant, E141G. Circ Cardiovasc Genet. 2016;9:136-146 pubmed publisher
    ..Genetic testing of CALM1-3 should be pursued for individuals with LQTS, especially those with early childhood cardiac arrest, extreme QT prolongation, and a negative family history. ..
  40. Soeiro de Souza M, Bio D, Dias V, Vieta E, Machado Vieira R, Moreno R. The CACNA1C risk allele selectively impacts on executive function in bipolar type I disorder. Acta Psychiatr Scand. 2013;128:362-9 pubmed publisher
    ..A single nucleotide polymorphism (SNP) (rs1006737) in the CACNA1C gene has been strongly associated with increased risk for Bipolar disorder (BD) in genome-wide association ..
  41. Zeng H, Roman M, Lis E, Lagrutta A, Sannajust F. Use of FDSS/?Cell imaging platform for preclinical cardiac electrophysiology safety screening of compounds in human induced pluripotent stem cell-derived cardiomyocytes. J Pharmacol Toxicol Methods. 2016;81:217-22 pubmed publisher
  42. Dressler F, Bodi I, Menza M, Moss R, Bugger H, Bode C, et al. Interregional electro-mechanical heterogeneity in the rabbit myocardium. Prog Biophys Mol Biol. 2017;130:344-355 pubmed publisher
    ..This pattern of apical mechanical dominance probably serves to increase pumping efficiency. ..
  43. Horváth B, Váczi K, Hegyi B, Gönczi M, Dienes B, Kistamás K, et al. Sarcolemmal Ca(2+)-entry through L-type Ca(2+) channels controls the profile of Ca(2+)-activated Cl(-) current in canine ventricular myocytes. J Mol Cell Cardiol. 2016;97:125-39 pubmed publisher
    ..Substantial activation of ICl(Ca) requires high Ca(2+) concentration in the dyadic clefts which can be effectively buffered by BAPTA, but not EGTA. ..
  44. VAN HEESC -. [A FORM OF TACHYCARDIA CAUSED BY DIGITALIS (PAROXYSMAL AURICULAR TACHYCARDIA WITH BLOCK)]. Geneeskd Gids. 1964;42:68-72 pubmed
  45. Jakobsson J, Pålsson E, Sellgren C, Rydberg F, Ekman A, Zetterberg H, et al. CACNA1C polymorphism and altered phosphorylation of tau in bipolar disorder. Br J Psychiatry. 2016;208:195-6 pubmed publisher
    ..studies and case-control studies have associated the single nucleotide polymorphism (SNP) rs1006737, situated in CACNA1C encoding the alpha 1C subunit of the L-type voltage-gated calcium channel, with bipolar disorder and other ..
  46. Jawinski P, Sander C, Mauche N, Spada J, Huang J, Schmidt A, et al. Brain Arousal Regulation in Carriers of Bipolar Disorder Risk Alleles. Neuropsychobiology. 2015;72:65-73 pubmed publisher
    ..Primary sample analyses revealed Bonferroni-adjusted significance for rs1006737 in CACNA1C (encoding a calcium channel subunit), with risk allele carriers exhibiting relatively steep brain arousal ..
  47. Córdova Palomera A, Fatjó Vilas M, Gastó C, Navarro V, Krebs M, Fañanás L. Genome-wide methylation study on depression: differential methylation and variable methylation in monozygotic twins. Transl Psychiatry. 2015;5:e557 pubmed publisher
    ..Complementarily, VMPs were located in genes such as CACNA1C, IGF2 and the p38 MAP kinase MAPK11, showing enrichment for biological processes such as glucocorticoid signaling...
  48. Hermosilla T, Encina M, Morales D, Moreno C, Conejeros C, Alfaro Valdés H, et al. Prolonged AT1R activation induces CaV1.2 channel internalization in rat cardiomyocytes. Sci Rep. 2017;7:10131 pubmed publisher
    ..This novel AT1R-dependent CaV1.2-trafficking modulation likely contributes to angiotensin II-mediated cardiac remodeling. ..
  49. Dietsche B, Backes H, Laneri D, Weikert T, Witt S, Rietschel M, et al. The impact of a CACNA1C gene polymorphism on learning and hippocampal formation in healthy individuals: a diffusion tensor imaging study. Neuroimage. 2014;89:256-61 pubmed publisher
    Genome-wide association studies have identified the CACNA1C single nucleotide polymorphism (SNP) rs1006737 as one of the most consistent genetic findings as susceptibility locus for major psychiatric disorders...
  50. Chen Y, Barajas Martinez H, Zhu D, Wang X, Chen C, Zhuang R, et al. Novel trigenic CACNA1C/DES/MYPN mutations in a family of hypertrophic cardiomyopathy with early repolarization and short QT syndrome. J Transl Med. 2017;15:78 pubmed publisher
    ..700G>A/p.E234K in DES, c.2966G>A/p.R989H in MYPN, and c.5918G>C/p.R1973P in CACNA1C. All mutations were also detected in his daughter with ER and mild myocardium hypertrophy...
  51. Yamanushi T, Boyett M, Yamamoto Y, Ohsaki H, Hirakawa E, Dobrzynski H. Comparison of formaldehyde and methanol fixatives used in the detection of ion channel proteins in isolated rat ventricular myocytes by immunofluorescence labelling and confocal microscopy. Folia Morphol (Warsz). 2015;74:258-61 pubmed publisher
    ..Kir6.2 at transverse tubules and Nav1.5 at sarcolemma were detected by FA but not by MeOH. It is suggested that both FA and MeOH fixation protocols should be used for the detection of cardiac ion channels by immunolabelling. ..
  52. Soeiro de Souza M, Lafer B, Moreno R, Nery F, Chile T, Chaim K, et al. The CACNA1C risk allele rs1006737 is associated with age-related prefrontal cortical thinning in bipolar I disorder. Transl Psychiatry. 2017;7:e1086 pubmed publisher
    Calcium channels control the inflow of calcium ions into cells and are involved in diverse cellular functions. The CACNA1C gene polymorphism rs1006737 A allele has been strongly associated with increased risk for bipolar disorder (BD) ..
  53. Phuapittayalert L, Saenganantakarn P, Supanpaiboon W, Cheunchoojit S, Hipkaeo W, Sakulsak N. Increasing CACNA1C expression in placenta containing high Cd level: an implication of Cd toxicity. Environ Sci Pollut Res Int. 2016;23:24592-24600 pubmed publisher
    ..05). In addition, the Ca channel alpha 1C (CACNA1C) mRNA and protein expressions were noticeably elevated in H-Cd group (p < 0.05)...
  54. Daschil N, Obermair G, Flucher B, Stefanova N, Hutter Paier B, Windisch M, et al. CaV1.2 calcium channel expression in reactive astrocytes is associated with the formation of amyloid-? plaques in an Alzheimer's disease mouse model. J Alzheimers Dis. 2013;37:439-51 pubmed publisher
  55. Zhang X, Zhang C, Wu Z, Wang Z, Peng D, Chen J, et al. Association of genetic variation in CACNA1C with bipolar disorder in Han Chinese. J Affect Disord. 2013;150:261-5 pubmed publisher
    ..of single nucleotide polymorphisms of the ?-1 C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with MDD and BD, suggesting CACNA1C as a promising candidate gene for susceptibility to mood disorders...
  56. Lu L, Zhang Q, Timofeyev V, Zhang Z, Young J, Shin H, et al. Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2. Circ Res. 2007;100:112-20 pubmed
  57. Fukuyama M, Ohno S, Wang Q, Kimura H, Makiyama T, Itoh H, et al. L-type calcium channel mutations in Japanese patients with inherited arrhythmias. Circ J. 2013;77:1799-806 pubmed
    ..We screened CACNA1C and CACNB2b in 312 probands and compared the clinical characteristics between probands with gene mutations in ..
  58. Fowler M, Colotti G, Chiancone E, Smith G, Fearon I. Sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit in rabbits. Exp Physiol. 2008;93:1233-8 pubmed publisher
    ..These data suggest that sorcin interacts with LTCC via its C-terminal domain, which alters current magnitude and tau(fast). These effects appear to be influenced by the prevailing experimental conditions...
  59. Santiago González D, Cheli V, Zamora N, Lama T, Spreuer V, Murphy G, et al. Conditional Deletion of the L-Type Calcium Channel Cav1.2 in NG2-Positive Cells Impairs Remyelination in Mice. J Neurosci. 2017;37:10038-10051 pubmed publisher
    ..These findings could lead to novel approaches for obtaining a better understanding of the factors that control OPC maturation in order to stimulate this pool of progenitors to replace myelin in demyelinating diseases. ..
  60. Wemhöner K, Friedrich C, Stallmeyer B, Coffey A, Grace A, Zumhagen S, et al. Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome. J Mol Cell Cardiol. 2015;80:186-95 pubmed publisher
    Gain-of-function mutations in CACNA1C, encoding the L-type Ca(2+) channel Cav1.2, cause Timothy syndrome (TS), a multi-systemic disorder with dysmorphic features, long-QT syndrome (LQTS) and autism spectrum disorders...
  61. Prieto M, Ryu E, Jenkins G, Batzler A, Nassan M, Cuellar Barboza A, et al. Leveraging electronic health records to study pleiotropic effects on bipolar disorder and medical comorbidities. Transl Psychiatry. 2016;6:e870 pubmed publisher
    ..The top association findings suggested that the BD risk alleles at SNP rs4765913 in CACNA1C gene and rs7042161 in SVEP1 may be associated with increased risk of 'cardiac dysrhythmias' (odds ratio (OR)=1...
  62. Wöber Bingöl C, Tropeano M, Karwautz A, Wagner G, Campos de Sousa S, Zesch H, et al. No association between bipolar disorder risk polymorphisms in ANK3 and CACNA1C and common migraine. Headache. 2011;51:796-803 pubmed publisher
    ..strong evidence of association between the polymorphisms rs10994336[T] in the ANK3 gene and rs1006737[A] in the CACNA1C gene and risk of bipolar disorder...
  63. Qian H, Patriarchi T, Price J, Matt L, Lee B, Nieves Cintrón M, et al. Phosphorylation of Ser1928 mediates the enhanced activity of the L-type Ca2+ channel Cav1.2 by the ?2-adrenergic receptor in neurons. Sci Signal. 2017;10: pubmed publisher
    ..2 and enhancement of its activity by the ?2-adrenergic receptor (?2AR)-cAMP-PKA cascade. Thus, there is an unexpected dichotomy in the control of Cav1.2 by PKA in cardiomyocytes and hippocampal neurons. ..
  64. Lancaster T, Heerey E, Mantripragada K, Linden D. CACNA1C risk variant affects reward responsiveness in healthy individuals. Transl Psychiatry. 2014;4:e461 pubmed publisher
    The variant at rs1006737 in the L-type voltage-gated calcium channel (alpha 1c subunit) CACNA1C gene is reliably associated with both bipolar disorder and schizophrenia...
  65. Xiong L, Kleerekoper Q, He R, Putkey J, Hamilton S. Sites on calmodulin that interact with the C-terminal tail of Cav1.2 channel. J Biol Chem. 2005;280:7070-9 pubmed
    ..In conclusion, Ca(2+)-calmodulin assumes a novel conformation when part of a complex with the C-terminal tail of the Ca(V)1.2 alpha(1) subunit that is not duplicated by synthetic peptides corresponding to the putative binding motifs. ..
  66. Chen X, Zhang X, Harris D, Piacentino V, Berretta R, Margulies K, et al. Reduced effects of BAY K 8644 on L-type Ca2+ current in failing human cardiac myocytes are related to abnormal adrenergic regulation. Am J Physiol Heart Circ Physiol. 2008;294:H2257-67 pubmed publisher
    ..Collectively, these results suggest that the decreased BAY K effects on LTCC in F HVMs are caused by increased basal channel activity, which should contribute to abnormal contractility reserve. ..
  67. Wessa M, Linke J, Witt S, Nieratschker V, Esslinger C, Kirsch P, et al. The CACNA1C risk variant for bipolar disorder influences limbic activity. Mol Psychiatry. 2010;15:1126-7 pubmed publisher
  68. Temme S, Murphy G. The L-type voltage-gated calcium channel CaV1.2 mediates fear extinction and modulates synaptic tone in the lateral amygdala. Learn Mem. 2017;24:580-588 pubmed publisher
    ..Together these data illustrate an important role of CaV1.2 in fear extinction and the synaptic regulation of activity within the amygdala. ..