Involvement of Voltage-Gated Ca2+ Channels in Autism Spectrum Disorders
Keywords:
autism spectrum disorders, Ca2 channels, Timothy syndrome, Fragile X sydromeAbstract
Substantial evidence suggests that mutated voltage-gated L-type Ca2+ channel subunit CaV1.2 (CACNAIC) is involved in pathophysiology of autism spectrum disorder (ASD), as exemplified by recent findings that mutated CACNAIC and other L-type Ca2+ channels play an important role in pathophysiology of Timothy Syndrome and Fragile X Syndrome, genetic syndromes of ASD. This review will focus on recent advances in our understanding of the genetic mutation of the CaV1.2 L-type channels in ASD, and highlight the potential roles of CaV1.2 channels in the pathogenesis of ASD.
References
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Barrett CF, Tsien RW. The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. Proc Natl Acad Sci USA. 2008;105(6):2157-2162.
Bhat S, Dao DT, Terrillion CE, et al. CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease. Prog Neurobiol. 2012; 99(1):1-14.
Breitenkamp AF, Matthes J, Nass RD, et al. Rare Mutations of CACNB2 Found in Autism Spectrum Disease-Affected Families Alter Calcium Channel Function. PLoS One. 2014; 9(4): e95579.
Chen L, Yun SW, Seto J, Liu W, Toth M. The fragile X mental retardation protein binds and regulates a novel class of mRNAs containing U rich target sequences. Neuroscience. 2003;120(4):1005-1017.
Consortium C-DGotPG. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013; 381(9875):1371-1379.
Ferreira MA, O'Donovan MC, Meng YA, et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet. 2008;40(9):1056-1058.
Franke B, Vasquez AA, Veltman JA, Brunner HG, 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(6):586-588.
Gershon ES, Grennan K, Busnello J, et al. A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CACNA1C in brain. Mol Psychiatry. 2014;19(8):890-894.
Guthrie W, Swineford LB, Wetherby AM, Lord C. Comparison of DSM-IV and DSM-5 factor structure models for toddlers with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2013; 52(8):797-805.
Harrington JW, Allen K. The clinician's guide to autism. Pediatr Rev. 2014;35(2):62-78.
Huerta M, Bishop SL, Duncan A, Hus V, Lord C. Application of DSM-5 criteria for autism spectrum disorder to three samples of children with DSM-IV diagnoses of pervasive developmental disorders. Am J Psychiatry. 2012;169(10):1056-1064.
Joksovic PM, Nelson MT, Jevtovic-Todorovic V, et al. CaV3.2 is the major molecular substrate for redox regulation of T-type Ca2+ channels in the rat and mouse thalamus. J Physiol. 2006;574(Pt 2):415-430.
Kempton MJ, Ruberto G, Vassos E, et al. Effects of the CACNA1C risk allele for bipolar disorder on cerebral gray matter volume in healthy individuals. Am J Psychiatry. 2009; 166(12):1413-1414.
King BH, Navot N, Bernier R, Webb SJ. Update on diagnostic classification in autism. Curr Opin Psychiatry. 2014;27(2):105-109.
Lu AT, Dai X, Martinez-Agosto JA, Cantor RM. Support for calcium channel gene defects in autism spectrum disorders. Mol Autism. 2012;3(1):18.
Maenner MJ, Rice CE, Arneson CL, et al. Potential impact of DSM-5 criteria on autism spectrum disorder prevalence estimates. JAMA Psychiatry. 2014;71(3):292-300.
Meredith RM, Holmgren CD, Weidum M, Burnashev N, Mansvelder HD. Increased threshold for spike-timing-dependent plasticity is caused by unreliable calcium signaling in mice lacking fragile X gene FMR1. Neuron. 2007;54(4):627-638.
Nyegaard M, Demontis D, Foldager L, et al. CACNA1C (rs1006737) is associated with schizophrenia. Mol Psychiatry. 2010;15(2):119-121.
Sadamatsu M, Kanai H, Xu X, Liu Y, Kato N. Review of animal models for autism: implication of thyroid hormone. Congenit Anom (Kyoto). 2006;46(1):1-9.
Sklar P, Smoller JW, Fan J, et al. Whole-genome association study of bipolar disorder. Mol Psychiatry. 2008;13(6):558-569.
Splawski I, Timothy KW, Decher N, et al. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci USA. 2005;102(23):8089-8096.
Splawski I, Timothy KW, Sharpe LM, et al. CaV1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004;119(1):19-31.
Splawski I, Yoo DS, Stotz SC, Cherry A, Clapham DE, Keating MT. CACNA1H mutations in autism spectrum disorders. J Biol Chem. 2006;281(31):22085-22091.
Wessa M, Linke J, Witt SH, et al. The CACNA1C risk variant for bipolar disorder influences limbic activity. Mol Psychiatry. 2010;15(12):1126-1127.
Wray NR, Pergadia ML, Blackwood DH, et al. Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned. Mol Psychiatry. 2010;17(1):36-48.
Young RL, Rodi ML. Redefining autism spectrum disorder using DSM-5: the implications of the proposed DSM-5 criteria for autism spectrum disorders. J Autism Dev Disord. 2013;44(4):758-765.
Barrett CF, Tsien RW. The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. Proc Natl Acad Sci USA. 2008;105(6):2157-2162.
Bhat S, Dao DT, Terrillion CE, et al. CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease. Prog Neurobiol. 2012; 99(1):1-14.
Breitenkamp AF, Matthes J, Nass RD, et al. Rare Mutations of CACNB2 Found in Autism Spectrum Disease-Affected Families Alter Calcium Channel Function. PLoS One. 2014; 9(4): e95579.
Chen L, Yun SW, Seto J, Liu W, Toth M. The fragile X mental retardation protein binds and regulates a novel class of mRNAs containing U rich target sequences. Neuroscience. 2003;120(4):1005-1017.
Consortium C-DGotPG. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013; 381(9875):1371-1379.
Ferreira MA, O'Donovan MC, Meng YA, et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet. 2008;40(9):1056-1058.
Franke B, Vasquez AA, Veltman JA, Brunner HG, 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(6):586-588.
Gershon ES, Grennan K, Busnello J, et al. A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CACNA1C in brain. Mol Psychiatry. 2014;19(8):890-894.
Guthrie W, Swineford LB, Wetherby AM, Lord C. Comparison of DSM-IV and DSM-5 factor structure models for toddlers with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2013; 52(8):797-805.
Harrington JW, Allen K. The clinician's guide to autism. Pediatr Rev. 2014;35(2):62-78.
Huerta M, Bishop SL, Duncan A, Hus V, Lord C. Application of DSM-5 criteria for autism spectrum disorder to three samples of children with DSM-IV diagnoses of pervasive developmental disorders. Am J Psychiatry. 2012;169(10):1056-1064.
Joksovic PM, Nelson MT, Jevtovic-Todorovic V, et al. CaV3.2 is the major molecular substrate for redox regulation of T-type Ca2+ channels in the rat and mouse thalamus. J Physiol. 2006;574(Pt 2):415-430.
Kempton MJ, Ruberto G, Vassos E, et al. Effects of the CACNA1C risk allele for bipolar disorder on cerebral gray matter volume in healthy individuals. Am J Psychiatry. 2009; 166(12):1413-1414.
King BH, Navot N, Bernier R, Webb SJ. Update on diagnostic classification in autism. Curr Opin Psychiatry. 2014;27(2):105-109.
Lu AT, Dai X, Martinez-Agosto JA, Cantor RM. Support for calcium channel gene defects in autism spectrum disorders. Mol Autism. 2012;3(1):18.
Maenner MJ, Rice CE, Arneson CL, et al. Potential impact of DSM-5 criteria on autism spectrum disorder prevalence estimates. JAMA Psychiatry. 2014;71(3):292-300.
Meredith RM, Holmgren CD, Weidum M, Burnashev N, Mansvelder HD. Increased threshold for spike-timing-dependent plasticity is caused by unreliable calcium signaling in mice lacking fragile X gene FMR1. Neuron. 2007;54(4):627-638.
Nyegaard M, Demontis D, Foldager L, et al. CACNA1C (rs1006737) is associated with schizophrenia. Mol Psychiatry. 2010;15(2):119-121.
Sadamatsu M, Kanai H, Xu X, Liu Y, Kato N. Review of animal models for autism: implication of thyroid hormone. Congenit Anom (Kyoto). 2006;46(1):1-9.
Sklar P, Smoller JW, Fan J, et al. Whole-genome association study of bipolar disorder. Mol Psychiatry. 2008;13(6):558-569.
Splawski I, Timothy KW, Decher N, et al. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci USA. 2005;102(23):8089-8096.
Splawski I, Timothy KW, Sharpe LM, et al. CaV1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004;119(1):19-31.
Splawski I, Yoo DS, Stotz SC, Cherry A, Clapham DE, Keating MT. CACNA1H mutations in autism spectrum disorders. J Biol Chem. 2006;281(31):22085-22091.
Wessa M, Linke J, Witt SH, et al. The CACNA1C risk variant for bipolar disorder influences limbic activity. Mol Psychiatry. 2010;15(12):1126-1127.
Wray NR, Pergadia ML, Blackwood DH, et al. Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned. Mol Psychiatry. 2010;17(1):36-48.
Young RL, Rodi ML. Redefining autism spectrum disorder using DSM-5: the implications of the proposed DSM-5 criteria for autism spectrum disorders. J Autism Dev Disord. 2013;44(4):758-765.
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Published
2014-07-31
How to Cite
Wang, A. L., Liu, F., & Wang, G. (2014). Involvement of Voltage-Gated Ca2+ Channels in Autism Spectrum Disorders. North American Journal of Medicine and Science, 7(3). Retrieved from https://najms.com/index.php/najms/article/view/158
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Review