Heyes S, Pratt WS, Rees E, Dahimene S, Ferron L, Owen MJ, et al. Genetic disruption of voltage-gated calcium channels in psychiatric and neurological disorders. Prog Neurobiol. 2015;134:36–54.
Trubetskoy V, Pardiñas AF, Qi T, Panagiotaropoulou G, Awasthi S, Bigdeli TB, et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature. 2022;604:502–8.
Mullins N, Forstner AJ, O’Connell KS, Coombes B, Coleman J, Qiao Z, et al. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nat Genet. 2021;53:817–29.
Colbourne L, Harrison PJ. Brain-penetrant calcium channel blockers are associated with a reduced incidence of neuropsychiatric disorders. Mol Psychiatry. 2022;27:3904–12.
Cipriani A, Saunders K, Attenburrow MJ, Stefaniak J, Panchal P, Stockton S, et al. A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future development. Mol Psychiatry. 2016;21:1324–32.
Harrison PJ, Husain SM, Lee H, Los Angeles A, Colbourne L, Mould A, et al. CACNA1C (Ca(V)1.2) and other L-type calcium channels in the pathophysiology and treatment of psychiatric disorders: advances from functional genomics and pharmacoepidemiology. Neuropharmacology. 2022;220:109262.
Hofmann F, Flockerzi V, Kahl S, Wegener JW. L-type CaV1.2 calcium channels: from in vitro findings to in vivo function. Physiol Rev. 2014;94:303–26.
Tang ZZ, Liang MC, Lu S, Yu D, Yu CY, Yue DT, 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.
Munyao W, Rahman MM, Sabzanov SA, Chu EH, Wang R, Wang Z, et al. Alternative splicing and CaV-associated channelopathies. Wiley Interdiscip Rev RNA. 2025;16:e70016.
Lipscombe D, Andrade A. Calcium channel CaValpha(1) splice isoforms – tissue specificity and drug action. Curr Mol Pharmacol. 2015;8:22–31.
Zühlke RD, Bouron A, Soldatov NM, 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.
Welling A, Ludwig A, Zimmer S, Klugbauer N, Flockerzi V, Hofmann F. Alternatively spliced IS6 segments of the alpha 1C gene determine the tissue-specific dihydropyridine sensitivity of cardiac and vascular smooth muscle L-type Ca2+ channels. Circ Res. 1997;81:526–32.
Lacinova L, Klugbauer N, Hofmann F. State- and isoform-dependent interaction of isradipine with the alpha1C L-type calcium channel. Pflug Arch. 2000;440:50–60.
Clark MB, Wrzesinski T, Garcia AB, Hall N, Kleinman JE, Hyde T, et al. Long-read sequencing reveals the complex splicing profile of the psychiatric risk gene CACNA1C in human brain. Mol Psychiatry. 2020;25:37–47.
Song JHT, Lowe CB, Kingsley DM. Characterization of a human-specific tandem repeat associated with bipolar disorder and schizophrenia. Am J Hum Genet. 2018;103:421–30.
Gershon ES, Grennan K, Busnello J, Badner JA, Ovsiew F, Memon S, 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;19:890–4.
Moya R, Wang X, Tsien RW, Maurano MT. Structure of a polymorphic repeat at the CACNA1C schizophrenia locus. Proc Natl Acad Sci USA. 2025;122:e2415650122.
Eckart N, Song Q, Yang R, Wang R, Zhu H, McCallion AS, et al. Functional characterization of schizophrenia-associated variation in CACNA1C. PLoS One. 2016;11:e0157086.
Bigos KL, Mattay VS, Callicott JH, Straub RE, Vakkalanka R, Kolachana B, et al. Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch Gen Psychiatry. 2010;67:939–45.
Yoshimizu T, Pan JQ, Mungenast AE, Madison JM, Su S, Ketterman J, et al. Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons. Mol Psychiatry. 2015;20:284.
Baker MR, Lee AS, Rajadhyaksha AM. L-type calcium channels and neuropsychiatric diseases: insights into genetic risk variant-associated genomic regulation and impact on brain development. Channels. 2023;17:2176984.
Xiao X, Chang H, Li M. Molecular mechanisms underlying noncoding risk variations in psychiatric genetic studies. Mol Psychiatry. 2017;22:497–511.
Tang ZZ, Hong X, Wang J, Soong TW. Signature combinatorial splicing profiles of rat cardiac- and smooth-muscle Cav1.2 channels with distinct biophysical properties. Cell Calcium. 2007;41:417–28.
The GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science. 2020;369:1318–30.
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15–21.
Jaffe AE, Shin J, Collado-Torres L, Leek JT, Tao R, Li C, et al. Developmental regulation of human cortex transcription and its clinical relevance at single base resolution. Nat Neurosci. 2015;18:154–61.
Dai B, Saada N, Echetebu C, Dettbarn C, Palade P. A new promoter for alpha1C subunit of human L-type cardiac calcium channel Ca(V)1.2. Biochem Biophys Res Commun. 2002;296:429–33.
Saada N, Dai B, Echetebu C, Sarna SK, Palade P. Smooth muscle uses another promoter to express primarily a form of human Cav1.2 L-type calcium channel different from the principal heart form. Biochem Biophys Res Commun. 2003;302:23–8.
Saada NI, Carrillo ED, Dai B, Wang WZ, Dettbarn C, Sanchez J, et al. Expression of multiple CaV1.2 transcripts in rat tissues mediated by different promoters. Cell Calcium. 2005;37:301–9.
Soldatov NM, Bouron A, Reuter H. Different voltage-dependent inhibition by dihydropyridines of human Ca2+ channel splice variants. J Biol Chem. 1995;270:10540–3.
Striessnig J, Grabner M, Mitterdorfer J, Hering S, Sinnegger MJ, Glossmann H. Structural basis of drug binding to L Ca2+ channels. Trends Pharmacol Sci. 1998;19:108–15.
Mazin PV, Khaitovich P, Cardoso-Moreira M, Kaessmann H. Alternative splicing during mammalian organ development. Nat Genet. 2021;53:925–34.
Benjamin KJM, Chen Q, Eagles NJ, Huuki-Myers LA, Collado-Torres L, Stolz JM, et al. Analysis of gene expression in the postmortem brain of neurotypical Black Americans reveals contributions of genetic ancestry. Nat Neurosci. 2024;27:1064–74.
Hall NAL, Carlyle BC, Haerty W, Tunbridge EM. Roadblock: improved annotations do not necessarily translate into new functional insights. Genome Biol. 2021;22:320.
Liao P, Yu D, Lu S, Tang Z, Liang MC, Zeng S, et al. Smooth muscle-selective alternatively spliced exon generates functional variation in Cav1.2 calcium channels. J Biol Chem. 2004;279:50329–35.
Zhang HY, Liao P, Wang JJ, Yu DJ, Soong TW. Alternative splicing modulates diltiazem sensitivity of cardiac and vascular smooth muscle Ca(v)1.2 calcium channels. Br J Pharmacol. 2010;160:1631–40.
Hu Z, Wang JW, Yu D, Soon JL, de Kleijn DP, Foo R, et al. Aberrant splicing promotes proteasomal degradation of L-type Ca(V)1.2 calcium channels by competitive binding for Ca(V)beta subunits in cardiac hypertrophy. Sci Rep. 2016;6:35247.
Cheng X, Liu J, Asuncion-Chin M, Blaskova E, Bannister JP, Dopico AM, et al. A novel Ca(V)1.2 N terminus expressed in smooth muscle cells of resistance size arteries modifies channel regulation by auxiliary subunits. J Biol Chem. 2007;282:29211–21.
Kanevsky N, Dascal N. Regulation of maximal open probability is a separable function of Ca(v)beta subunit in L-type Ca2+ channel, dependent on NH2 terminus of alpha1C (Ca(v)1.2alpha). J Gen Physiol. 2006;128:15–36.
Shistik E, Ivanina T, Blumenstein Y, Dascal N. Crucial role of N terminus in function of cardiac L-type Ca2+ channel and its modulation by protein kinase C. J Biol Chem. 1998;273:17901–9.
Kawaji H, Frith MC, Katayama S, Sandelin A, Kai C, Kawai J, et al. Dynamic usage of transcription start sites within core promoters. Genome Biol. 2006;7:R118.
Schultz D, Mikala G, Yatani A, Engle DB, Iles DE, Segers B, et al. Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart. Proc Natl Acad Sci USA. 1993;90:6228–32.
Mikala G, Klöckner U, Varadi M, Eisfeld J, Schwartz A, Varadi G. cAMP-dependent phosphorylation sites and macroscopic activity of recombinant cardiac L-type calcium channels. Mol Cell Biochem. 1998;185:95–109.
Allen TJ, Mikala G, Wu X, Dolphin AC. Effects of 2,3-butanedione monoxime (BDM) on calcium channels expressed in Xenopus oocytes. J Physiol. 1998;508(Pt 1):1–14.
Bahinski A, Yatani A, Mikala G, Tang S, Yamamoto S, Schwartz A. Charged amino acids near the pore entrance influence ion-conduction of a human L-type cardiac calcium channel. Mol Cell Biochem. 1997;166:125–34.
Fearon IM, Palmer AC, Balmforth AJ, Ball SG, Mikala G, Schwartz A, et al. Hypoxia inhibits the recombinant alpha 1C subunit of the human cardiac L-type Ca2+ channel. J Physiol. 1997;500(Pt 3):551–6.
Oz S, Tsemakhovich V, Christel CJ, Lee A, Dascal N. CaBP1 regulates voltage-dependent inactivation and activation of Ca(V)1.2 (L-type) calcium channels. J Biol Chem. 2011;286:13945–53.
Liu Z, Vogel HJ. Structural basis for the regulation of L-type voltage-gated calcium channels: interactions between the N-terminal cytoplasmic domain and Ca(2+)-calmodulin. Front Mol Neurosci. 2012;5:38.
Dick IE, Tadross MR, Liang H, Tay LH, Yang W, Yue DT. A modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels. Nature. 2008;451:830–4.
Chen Z, Mondal A, Abderemane-Ali F, Jang S, Niranjan S, Montaño JL, et al. EMC chaperone-Ca(V) structure reveals an ion channel assembly intermediate. Nature. 2023;619:410–9.