{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:24Z","timestamp":1787027844544,"version":"build-2736575974"},"reference-count":136,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation Intermediate Basic Science Research Fellowship","doi-asserted-by":"publisher","award":["FS\/17\/56\/32925"],"award-info":[{"award-number":["FS\/17\/56\/32925"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation Intermediate Basic Science Research Fellowship","doi-asserted-by":"publisher","award":["FS\/EXT\/22\/35014"],"award-info":[{"award-number":["FS\/EXT\/22\/35014"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation non-clinical PhD studentship","doi-asserted-by":"publisher","award":["FS\/PhD\/20\/29025"],"award-info":[{"award-number":["FS\/PhD\/20\/29025"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation non-clinical PhD studentship","doi-asserted-by":"publisher","award":["FS\/PhD\/22\/29339"],"award-info":[{"award-number":["FS\/PhD\/22\/29339"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BB\/V002767\/1"],"award-info":[{"award-number":["BB\/V002767\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust 4-year PhD studentship program","doi-asserted-by":"publisher","award":["102172\/B\/13\/Z"],"award-info":[{"award-number":["102172\/B\/13\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Liverpool, Institute of Translational Medicine PhD studentship"},{"name":"British Heart Foundation Intermediate Basic Science Research Fellowship","award":["FS\/IBSRF\/21\/25071"],"award-info":[{"award-number":["FS\/IBSRF\/21\/25071"]}]},{"name":"Heart Research Wales"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Calmodulin (CaM) plays a central role in cardiac excitation\u2013contraction coupling by regulating ion channels, including the L-type calcium (Ca2+) channel Cav1.2 and the voltage-gated potassium (K+) channel Kv7.1. Mutations in CaM are linked to severe arrhythmogenic disorders such as Long QT syndrome (LQTS), yet the molecular mechanisms remain incompletely understood. Here, we investigate the structural and functional consequences of the arrhythmia-associated CaM variant D133H. Biophysical analysis revealed that D133H destabilises Ca2+ binding at the C-terminal lobe of CaM, altering its Ca2+-dependent conformational changes. Electrophysiological recordings demonstrated that CaM D133H impairs Ca2+-dependent inactivation (CDI) of Cav1.2, prolonging Ca2+ influx, while also reducing activation of Kv7.1, thereby limiting repolarising K+ currents. Together, these dual defects converge to prolong action potential duration, providing a mechanistic basis for arrhythmogenesis in LQTS. Our findings establish that CaM D133H perturbs both Ca2+ and K+ channel regulation, highlighting a shared pathway by which calmodulinopathy mutations disrupt cardiac excitability.<\/jats:p>","DOI":"10.3390\/cells14221763","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:56:27Z","timestamp":1762858587000},"page":"1763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Calmodulin D133H Disrupts Cav1.2 and Kv7.1 Regulation to Prolong Cardiac Action Potentials in Long QT Syndrome"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3885-2500","authenticated-orcid":false,"given":"Nitika","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9557-9403","authenticated-orcid":false,"given":"Liam F.","family":"McCormick","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, UK"},{"name":"Genomic Diagnostics Laboratory, Manchester Centre for Genomic Medicine, St Mary\u2019s Hospital, Manchester M13 9WL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella M. B.","family":"Richards","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty","family":"Wadmore","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa S.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Kirilenko","sequence":"additional","affiliation":[{"name":"School of Biosciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF10 3AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5580-2156","authenticated-orcid":false,"given":"Ewan D.","family":"Fowler","sequence":"additional","affiliation":[{"name":"School of Biosciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF10 3AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Dart","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3743-1886","authenticated-orcid":false,"given":"Nordine","family":"Helassa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1161\/CIRCULATIONAHA.109.863209","article-title":"Prevalence of the congenital long-QT syndrome","volume":"120","author":"Schwartz","year":"2009","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.1113\/jphysiol.2013.254920","article-title":"Long QT syndrome: Beyond the causal mutation","volume":"591","author":"Amin","year":"2013","journal-title":"J. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1007\/s00246-019-02151-x","article-title":"Long QT Syndrome: Genetics and Future Perspective","volume":"40","author":"Wallace","year":"2019","journal-title":"Pediatr. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1161\/01.CIR.94.8.1996","article-title":"Multiple mechanisms in the long-QT syndrome. Current knowledge, gaps, and future directions. The SADS Foundation Task Force on LQTS","volume":"94","author":"Roden","year":"1996","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1161\/CIRCEP.111.962019","article-title":"Long-QT syndrome: From genetics to management","volume":"5","author":"Schwartz","year":"2012","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1136\/heartjnl-2020-318259","article-title":"Diagnosis, management and therapeutic strategies for congenital long QT syndrome","volume":"108","author":"Wilde","year":"2022","journal-title":"Heart"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1161\/CIRCULATIONAHA.119.043132","article-title":"An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome","volume":"141","author":"Adler","year":"2020","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.cjco.2020.09.023","article-title":"Novel G1481V and Q1491H SCN5A Mutations Linked to Long QT Syndrome Destabilize the Nav1.5 Inactivation State","volume":"3","author":"Plumereau","year":"2021","journal-title":"CJC Open"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ijcard.2016.06.081","article-title":"Novel long QT syndrome-associated missense mutation, L762F, in CACNA1C-encoded L-type calcium channel imparts a slower inactivation tau and increased sustained and window current","volume":"220","author":"Landstrom","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1161\/CIRCGENETICS.113.000138","article-title":"Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long QT syndrome","volume":"6","author":"Boczek","year":"2013","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1093\/europace\/euu063","article-title":"Long QT syndrome type 8: Novel CACNA1C mutations causing QT prolongation and variant phenotypes","volume":"16","author":"Fukuyama","year":"2014","journal-title":"Europace"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e00476","DOI":"10.1002\/mgg3.476","article-title":"Penetrance and expressivity of the R858H CACNA1C variant in a five-generation pedigree segregating an arrhythmogenic channelopathy","volume":"7","author":"Gardner","year":"2019","journal-title":"Mol. Genet. Genomic Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"17055","DOI":"10.1016\/S0021-9258(18)37497-0","article-title":"Multiple divergent mRNAs code for a single human calmodulin","volume":"263","author":"Fischer","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1093\/cvr\/cvaf059","article-title":"Distinct intracellular spatiotemporal expression of Calmodulin genes underlies functional diversity of Calmodulin-dependent signalling in cardiac myocytes","volume":"121","author":"Bogdanov","year":"2025","journal-title":"Cardiovasc. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1161\/CIRCULATIONAHA.120.046450","article-title":"Complex Arrhythmia Syndrome in a Knock-In Mouse Model Carrier of the N98S Calm1 Mutation","volume":"142","author":"Tsai","year":"2020","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1161\/CIRCULATIONAHA.112.001216","article-title":"Calmodulin mutations associated with recurrent cardiac arrest in infants","volume":"127","author":"Crotti","year":"2013","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Negi, S. (2014). Effect of Calcium Ion Removal, Ionic Strength, and Temperature on the Conformation Change in Calmodulin Protein at Physiological pH. J. Biophys., 2014.","DOI":"10.1155\/2014\/329703"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/nsb0995-758","article-title":"Calcium-induced conformational transition revealed by the solution structure of apo calmodulin","volume":"2","author":"Zhang","year":"1995","journal-title":"Nat. Struct. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/0022-2836(92)90324-D","article-title":"Calmodulin structure refined at 1.7 A resolution","volume":"228","author":"Chattopadhyaya","year":"1992","journal-title":"J. Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.str.2012.03.019","article-title":"Structural basis for calmodulin as a dynamic calcium sensor","volume":"20","author":"Zhang","year":"2012","journal-title":"Structure"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5511","DOI":"10.1111\/febs.12337","article-title":"Calmodulin in a heartbeat","volume":"280","author":"Sorensen","year":"2013","journal-title":"FEBS J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4244","DOI":"10.1021\/bi9718200","article-title":"Interactions between domains of apo calmodulin alter calcium binding and stability","volume":"37","author":"Sorensen","year":"1998","journal-title":"Biochemistry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E1216","DOI":"10.1073\/pnas.1600385113","article-title":"Conserved properties of individual Ca2+-binding sites in calmodulin","volume":"113","author":"Halling","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7617","DOI":"10.1021\/bi9800449","article-title":"Ca2+ coordination to backbone carbonyl oxygen atoms in calmodulin and other EF-hand proteins: 15N chemical shifts as probes for monitoring individual-site Ca2+ coordination","volume":"37","author":"Biekofsky","year":"1998","journal-title":"Biochemistry"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kameyama, M., Minobe, E., Shao, D., Xu, J., Gao, Q., and Hao, L. (2023). Regulation of Cardiac CaV1.2 Channels by Calmodulin. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076409"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/S0962-8924(00)01800-6","article-title":"Calmodulin: A prototypical calcium sensor","volume":"10","author":"Chin","year":"2000","journal-title":"Trends Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1085\/jgp.201611721","article-title":"Calmodulin limits pathogenic Na+ channel persistent current","volume":"149","author":"Yan","year":"2017","journal-title":"J. Gen. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e2025085118","DOI":"10.1073\/pnas.2025085118","article-title":"Elementary mechanisms of calmodulin regulation of NaV1.5 producing divergent arrhythmogenic phenotypes","volume":"118","author":"Kang","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1161\/CIRCRESAHA.114.302857","article-title":"Cardiac myocyte Z-line calmodulin is mainly RyR2-bound, and reduction is arrhythmogenic and occurs in heart failure","volume":"114","author":"Yang","year":"2014","journal-title":"Circ. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.neuron.2018.01.035","article-title":"A Calmodulin C-Lobe Ca2+-Dependent Switch Governs Kv7 Channel Function","volume":"97","author":"Chang","year":"2018","journal-title":"Neuron"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e14210","DOI":"10.14814\/phy2.14210","article-title":"Impact of arrhythmogenic calmodulin variants on small conductance Ca2+-activated K+ (SK3) channels","volume":"7","author":"Saljic","year":"2019","journal-title":"Physiol. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1006\/jmcc.2002.2038","article-title":"Calcium, calmodulin, and calcium-calmodulin kinase II: Heartbeat to heartbeat and beyond","volume":"34","author":"Maier","year":"2002","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.cardiores.2006.10.019","article-title":"Calmodulin and CaMKII as molecular switches for cardiac ion channels","volume":"73","author":"Pitt","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev.physiol.70.113006.100455","article-title":"Calcium cycling and signaling in cardiac myocytes","volume":"70","author":"Bers","year":"2008","journal-title":"Annu. Rev. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0092-8674(01)00243-4","article-title":"Molecular and cellular mechanisms of cardiac arrhythmias","volume":"104","author":"Keating","year":"2001","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0896-6273(91)90073-9","article-title":"Distinct calcium channels are generated by alternative splicing and are differentially expressed in the mammalian CNS","volume":"7","author":"Snutch","year":"1991","journal-title":"Neuron"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1152\/physrev.00016.2013","article-title":"L-type CaV1.2 calcium channels: From in vitro findings to in vivo function","volume":"94","author":"Hofmann","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hu, Z., Liang, M.C., and Soong, T.W. (2017). Alternative Splicing of L-type CaV1.2 Calcium Channels: Implications in Cardiovascular Diseases. Genes, 8.","DOI":"10.3390\/genes8120344"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/nature06529","article-title":"A modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels","volume":"451","author":"Dick","year":"2008","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0896-6273(03)00395-7","article-title":"FRET two-hybrid mapping reveals function and location of L-type Ca2+ channel CaM preassociation","volume":"39","author":"Erickson","year":"2003","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0896-6273(01)00438-X","article-title":"Preassociation of calmodulin with voltage-gated Ca2+ channels revealed by FRET in single living cells","volume":"31","author":"Erickson","year":"2001","journal-title":"Neuron"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bartels, P., Salveson, I., Coleman, A.M., Anderson, D.E., Jeng, G., Estrada-Tobar, Z.M., Man, K.N.M., Yu, Q., Kuzmenkina, E., and Nieves-Cintron, M. (2022). Half-calcified calmodulin promotes basal activity and inactivation of the L-type calcium channel CaV1.2. J. Biol. Chem., 298.","DOI":"10.1101\/2022.06.24.497440"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/j.str.2005.09.021","article-title":"Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac CaV1.2 calcium channel","volume":"13","author":"Fallon","year":"2005","journal-title":"Structure"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1038\/nsmb1027","article-title":"Insights into voltage-gated calcium channel regulation from the structure of the CaV1.2 IQ domain-Ca2+\/calmodulin complex","volume":"12","author":"Chatelain","year":"2005","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1038\/emboj.2010.260","article-title":"Multiple C-terminal tail Ca2+\/CaMs regulate CaV1.2 function but do not mediate channel dimerization","volume":"29","author":"Kim","year":"2010","journal-title":"EMBO J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1016\/S0006-3495(03)74586-X","article-title":"Apocalmodulin and Ca2+ calmodulin-binding sites on the CaV1.2 channel","volume":"85","author":"Tang","year":"2003","journal-title":"Biophys. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"337","DOI":"10.4161\/chan.3.5.9686","article-title":"Characterization of the calmodulin-binding site in the N terminus of CaV1.2","volume":"3","author":"Benmocha","year":"2009","journal-title":"Channels"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Taiakina, V., Boone, A.N., Fux, J., Senatore, A., Weber-Adrian, D., Guillemette, J.G., and Spafford, J.D. (2013). The calmodulin-binding, short linear motif, NSCaTE is conserved in L-type channel ancestors of vertebrate CaV1.2 and CaV1.3 channels. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061765"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1254\/jphs.09342FP","article-title":"Interactions of calmodulin with the multiple binding sites of CaV1.2 Ca2+ channels","volume":"112","author":"Asmara","year":"2010","journal-title":"J. Pharmacol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Liu, Z., and Vogel, H.J. (2012). Structural basis for the regulation of L-type voltage-gated calcium channels: Interactions between the N-terminal cytoplasmic domain and Ca2+-calmodulin. Front. Mol. Neurosci., 5.","DOI":"10.3389\/fnmol.2012.00038"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/20200","article-title":"Calmodulin supports both inactivation and facilitation of L-type calcium channels","volume":"399","author":"Zuhlke","year":"1999","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"21121","DOI":"10.1074\/jbc.M002986200","article-title":"Ca2+-sensitive inactivation and facilitation of L-type Ca2+ channels both depend on specific amino acid residues in a consensus calmodulin-binding motif in the(alpha)1C subunit","volume":"275","author":"Zuhlke","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1073\/pnas.95.6.3287","article-title":"Ca2+-sensitive inactivation of L-type Ca2+ channels depends on multiple cytoplasmic amino acid sequences of the alpha1C subunit","volume":"95","author":"Zuhlke","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0896-6273(00)80709-6","article-title":"Calmodulin is the Ca2+ sensor for Ca2+ -dependent inactivation of L-type calcium channels","volume":"22","author":"Peterson","year":"1999","journal-title":"Neuron"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.hrthm.2009.12.017","article-title":"Structural basis for K(V)7.1-KCNE(x) interactions in the I(Ks) channel complex","volume":"7","author":"Lundby","year":"2010","journal-title":"Heart Rhythm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"E869","DOI":"10.1073\/pnas.1612622114","article-title":"Competition of calcified calmodulin N lobe and PIP2 to an LQT mutation site in Kv7.1 channel","volume":"114","author":"Tobelaim","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.cell.2017.05.019","article-title":"Cryo-EM Structure of a KCNQ1\/CaM Complex Reveals Insights into Congenital Long QT Syndrome","volume":"169","author":"Sun","year":"2017","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/j.str.2014.07.016","article-title":"Structural basis of a Kv7.1 potassium channel gating module: Studies of the intracellular c-terminal domain in complex with calmodulin","volume":"22","author":"Sachyani","year":"2014","journal-title":"Structure"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1161\/01.RES.0000218863.44140.f2","article-title":"KCNQ1 assembly and function is blocked by long-QT syndrome mutations that disrupt interaction with calmodulin","volume":"98","author":"Ghosh","year":"2006","journal-title":"Circ. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.coph.2013.12.004","article-title":"Recent molecular insights from mutated IKS channels in cardiac arrhythmia","volume":"15","author":"Dvir","year":"2014","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e011387","DOI":"10.1161\/CIRCEP.122.011387","article-title":"Novel Calmodulin Variant p.E46K Associated With Severe Catecholaminergic Polymorphic Ventricular Tachycardia Produces Robust Arrhythmogenicity in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes","volume":"16","author":"Gao","year":"2023","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Jimenez-Jaimez, J., Palomino Doza, J., Ortega, A., Macias-Ruiz, R., Perin, F., Rodriguez-Vazquez del Rey, M.M., Ortiz-Genga, M., Monserrat, L., Barriales-Villa, R., and Blanca, E. (2016). Calmodulin 2 Mutation N98S Is Associated with Unexplained Cardiac Arrest in Infants Due to Low Clinical Penetrance Electrical Disorders. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153851"},{"key":"ref_63","first-page":"8","article-title":"Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V) Activates Arrhythmogenic Ca Waves and Sparks","volume":"9","author":"Boczek","year":"2016","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.hrcr.2016.09.004","article-title":"A novel de novo calmodulin mutation in a 6-year-old boy who experienced an aborted cardiac arrest","volume":"3","author":"Takahashi","year":"2017","journal-title":"HeartRhythm Case Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/europace\/euaa272","article-title":"Infanticide vs. inherited cardiac arrhythmias","volume":"23","author":"Brohus","year":"2021","journal-title":"Europace"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.hrthm.2014.10.035","article-title":"CALM3 mutation associated with long QT syndrome","volume":"12","author":"Reed","year":"2015","journal-title":"Heart Rhythm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1161\/CIRCGEN.119.002581","article-title":"Genetic Mosaicism in Calmodulinopathy","volume":"12","author":"Wren","year":"2019","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e002255","DOI":"10.1161\/CIRCGEN.118.002255","article-title":"Novel Association of a De Novo CALM2 Mutation With Long QT Syndrome and Hypertrophic Cardiomyopathy","volume":"11","author":"Zahavich","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1016\/j.hrthm.2016.06.038","article-title":"Novel calmodulin mutations associated with congenital long QT syndrome affect calcium current in human cardiomyocytes","volume":"13","author":"Pipilas","year":"2016","journal-title":"Heart Rhythm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e010572","DOI":"10.1161\/CIRCEP.121.010572","article-title":"Novel CALM3 Variant Causing Calmodulinopathy With Variable Expressivity in a 4-Generation Family","volume":"15","author":"Kato","year":"2022","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"ytae340","DOI":"10.1093\/ehjcr\/ytae340","article-title":"A rare case report of catecholaminergic polymorphic ventricular tachycardia with an uncommon CALM2 mutation","volume":"8","author":"Ding","year":"2024","journal-title":"Eur. Heart J. Case Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.ajhg.2012.08.015","article-title":"Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death","volume":"91","author":"Nyegaard","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1093\/eurheartj\/ehz311","article-title":"Calmodulin mutations and life-threatening cardiac arrhythmias: Insights from the International Calmodulinopathy Registry","volume":"40","author":"Crotti","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.jacc.2013.07.091","article-title":"A mutation in CALM1 encoding calmodulin in familial idiopathic ventricular fibrillation in childhood and adolescence","volume":"63","author":"Marsman","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4822","DOI":"10.15419\/bmrat.v9i1.719","article-title":"Long QT syndrome: Identification of a novel de novo mutation of calmodulin in a newborn girl","volume":"9","author":"Nguyen","year":"2022","journal-title":"Biomed. Res. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.hrcr.2016.02.002","article-title":"Novel CALM3 mutations in pediatric long QT syndrome patients support a CALM3-specific calmodulinopathy","volume":"2","author":"Chaix","year":"2016","journal-title":"HeartRhythm Case Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/CIRCGENETICS.115.001323","article-title":"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","volume":"9","author":"Boczek","year":"2016","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1161\/CIRCGENETICS.113.000459","article-title":"Novel calmodulin mutations associated with congenital arrhythmia susceptibility","volume":"7","author":"Makita","year":"2014","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1111\/ped.13959","article-title":"Long QT syndrome with a de novo CALM2 mutation in a 4-year-old boy","volume":"61","author":"Fujita","year":"2019","journal-title":"Pediatr. Int."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4554","DOI":"10.1111\/febs.14969","article-title":"Diminished inhibition and facilitated activation of RyR2-mediated Ca2+ release is a common defect of arrhythmogenic calmodulin mutations","volume":"286","author":"Sondergaard","year":"2019","journal-title":"FEBS J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"jcs258796","DOI":"10.1242\/jcs.258796","article-title":"CPVT-associated calmodulin variants N53I and A102V dysregulate Ca2+ signalling via different mechanisms","volume":"135","author":"Prakash","year":"2022","journal-title":"J. Cell Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/nyas.14033","article-title":"Arrhythmogenic calmodulin E105A mutation alters cardiac RyR2 regulation leading to cardiac dysfunction in zebrafish","volume":"1448","author":"Thanassoulas","year":"2019","journal-title":"Ann. N. Y Acad. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"26151","DOI":"10.1074\/jbc.M115.676627","article-title":"Arrhythmogenic Calmodulin Mutations Affect the Activation and Termination of Cardiac Ryanodine Receptor-mediated Ca2+ Release","volume":"290","author":"Sondergaard","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1016\/j.bbagen.2015.07.001","article-title":"Distinctive malfunctions of calmodulin mutations associated with heart RyR2-mediated arrhythmic disease","volume":"1850","author":"Vassilakopoulou","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1161\/CIRCRESAHA.114.303391","article-title":"Divergent regulation of ryanodine receptor 2 calcium release channels by arrhythmogenic human calmodulin missense mutants","volume":"114","author":"Hwang","year":"2014","journal-title":"Circ. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7620","DOI":"10.1074\/jbc.RA120.013430","article-title":"The arrhythmogenic N53I variant subtly changes the structure and dynamics in the calmodulin N-terminal domain, altering its interaction with the cardiac ryanodine receptor","volume":"295","author":"Holt","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"C991","DOI":"10.1152\/ajpcell.00019.2020","article-title":"The LQT-associated calmodulin mutant E141G induces disturbed Ca2+-dependent binding and a flickering gating mode of the CaV1.2 channel","volume":"318","author":"Su","year":"2020","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Prakash, O., Gupta, N., Milburn, A., McCormick, L., Deugi, V., Fisch, P., Wyles, J., Thomas, N.L., Antonyuk, S., and Dart, C. (2023). Calmodulin variant E140G associated with long QT syndrome impairs CaMKIIdelta autophosphorylation and L-type calcium channel inactivation. J. Biol. Chem., 299.","DOI":"10.1016\/j.jbc.2022.102777"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e14276","DOI":"10.1111\/apha.14276","article-title":"Arrhythmogenic calmodulin variants D131E and Q135P disrupt interaction with the L-type voltage-gated Ca2+ channel (CaV1.2) and reduce Ca2+-dependent inactivation","volume":"241","author":"Gupta","year":"2025","journal-title":"Acta Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.yjmcc.2014.04.022","article-title":"Calmodulin mutations associated with long QT syndrome prevent inactivation of cardiac L-type Ca2+ currents and promote proarrhythmic behavior in ventricular myocytes","volume":"74","author":"Limpitikul","year":"2014","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1093\/hmg\/ddx073","article-title":"Allele-specific ablation rescues electrophysiological abnormalities in a human iPS cell model of long-QT syndrome with a CALM2 mutation","volume":"26","author":"Yamamoto","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"E10556","DOI":"10.1073\/pnas.1808733115","article-title":"Arrhythmia mutations in calmodulin cause conformational changes that affect interactions with the cardiac voltage-gated calcium channel","volume":"115","author":"Wang","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1113\/JP279307","article-title":"Arrhythmia mutations in calmodulin can disrupt cooperativity of Ca2+ binding and cause misfolding","volume":"598","author":"Wang","year":"2020","journal-title":"J. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1074\/jbc.M116.766253","article-title":"The Arrhythmogenic Calmodulin p.Phe142Leu Mutation Impairs C-domain Ca2+ Binding but Not Calmodulin-dependent Inhibition of the Cardiac Ryanodine Receptor","volume":"292","author":"Sondergaard","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.1113\/JP284994","article-title":"Long QT syndrome-associated calmodulin variants disrupt the activity of the slowly activating delayed rectifier potassium channel","volume":"601","author":"McCormick","year":"2023","journal-title":"J. Physiol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Da\u2019as, S.I., Thanassoulas, A., Calver, B.L., Saleh, A., Abdelrahman, D., Hasan, W., Safieh-Garabedian, B., Kontogianni, I., Nasrallah, G.K., and Nounesis, G. (2024). Divergent Biochemical Properties and Disparate Impact of Arrhythmogenic Calmodulin Mutations on Zebrafish Cardiac Function. J. Cell Biochem., 125.","DOI":"10.1002\/jcb.30619"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/HCO.0000000000000808","article-title":"Calmodulinopathies: Throwing back the veil on the newest life-threatening genetic arrhythmia syndrome","volume":"36","author":"Etheridge","year":"2021","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e004542","DOI":"10.1161\/CIRCGEN.124.004542","article-title":"Role of Calmodulin in Cardiac Disease: Insights on Genotype and Phenotype","volume":"17","author":"Schwartz","year":"2024","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"339","DOI":"10.4103\/tcmj.tcmj_182_20","article-title":"Calmodulinopathy in inherited arrhythmia syndromes","volume":"33","author":"Tsai","year":"2021","journal-title":"Tzu Chi Med. J."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Chazin, W.J., and Johnson, C.N. (2020). Calmodulin Mutations Associated with Heart Arrhythmia: A Status Report. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041418"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2165278","DOI":"10.1080\/19336950.2023.2165278","article-title":"Calmodulin Mutations in Human Disease","volume":"17","author":"Hussey","year":"2023","journal-title":"Channels"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"pgad335","DOI":"10.1093\/pnasnexus\/pgad335","article-title":"Arrhythmia-associated calmodulin variants interact with KCNQ1 to confer aberrant membrane trafficking and function","volume":"2","author":"Kang","year":"2023","journal-title":"PNAS Nexus"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.yjmcc.2025.07.014","article-title":"Compromised repolarization reserve in a murine model of catecholaminergic polymorphic ventricular tachycardia caused by RyR2-R420Q mutation","volume":"206","author":"Zissimopoulos","year":"2025","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/384080a0","article-title":"Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel","volume":"384","author":"Sanguinetti","year":"1996","journal-title":"Nature"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.ceca.2006.07.011","article-title":"Free and bound intracellular calmodulin measurements in cardiac myocytes","volume":"41","author":"Wu","year":"2007","journal-title":"Cell Calcium"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.yjmcc.2015.02.027","article-title":"Impaired calcium-calmodulin-dependent inactivation of CaV1.2 contributes to loss of sarcoplasmic reticulum calcium release refractoriness in mice lacking calsequestrin 2","volume":"82","author":"Kryshtal","year":"2015","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1113\/jphysiol.2002.019729","article-title":"Voltage- and cation-dependent inactivation of L-type Ca2+ channel currents in guinea-pig ventricular myocytes","volume":"541","author":"Findlay","year":"2002","journal-title":"J. Physiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-374841-6.00001-3","article-title":"A practical guide to the preparation of Ca2+ buffers","volume":"99","author":"Bers","year":"2010","journal-title":"Methods Cell Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"28545","DOI":"10.1074\/jbc.M204130200","article-title":"The identification and characterization of a noncontinuous calmodulin-binding site in noninactivating voltage-dependent KCNQ potassium channels","volume":"277","author":"Villarroel","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/prot.20449","article-title":"The CCPN data model for NMR spectroscopy: Development of a software pipeline","volume":"59","author":"Vranken","year":"2005","journal-title":"Proteins"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.pbiomolbio.2014.06.008","article-title":"Systems approach to the study of stretch and arrhythmias in right ventricular failure induced in rats by monocrotaline","volume":"115","author":"Benoist","year":"2014","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e003206","DOI":"10.1161\/CIRCEP.115.003206","article-title":"Prevalence of Microvolt T-Wave Alternans in Patients With Long QT Syndrome and Its Association With Torsade de Pointes","volume":"9","author":"Takasugi","year":"2016","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1073\/pnas.1715997115","article-title":"STAC proteins associate to the IQ domain of CaV1.2 and inhibit calcium-dependent inactivation","volume":"115","author":"Campiglio","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1093\/eurheartj\/ehv316","article-title":"2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC)","volume":"36","author":"Priori","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14740\/jocmr4823","article-title":"Sudden Cardiac Death in Young Individuals: A Current Review of Evaluation, Screening and Prevention","volume":"15","author":"Abbas","year":"2023","journal-title":"J. Clin. Med. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00018-022-04165-w","article-title":"Alterations in calmodulin-cardiac ryanodine receptor molecular recognition in congenital arrhythmias","volume":"79","author":"Barracchia","year":"2022","journal-title":"Cell Mol. Life Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00439-023-02629-y","article-title":"Impact of calmodulin missense variants associated with congenital arrhythmia on the thermal stability and the degree of unfolding","volume":"144","author":"Marino","year":"2025","journal-title":"Hum. Genet."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/cvr\/cvx006","article-title":"Elucidating arrhythmogenic mechanisms of long-QT syndrome CALM1-F142L mutation in patient-specific induced pluripotent stem cell-derived cardiomyocytes","volume":"113","author":"Rocchetti","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"H33-44","DOI":"10.1152\/ajpheart.00232.2009","article-title":"Beta-adrenergic modulation of arrhythmogenesis and identification of targeted sites of antiarrhythmic therapy in Timothy (LQT8) syndrome: A theoretical study","volume":"298","author":"Sung","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1161\/01.RES.79.1.79","article-title":"Developmental changes in the delayed rectifier K+ channels in mouse heart","volume":"79","author":"Wang","year":"1996","journal-title":"Circ. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1161\/CIRCRESAHA.117.312257","article-title":"Late Ca2+ Sparks and Ripples During the Systolic Ca2+ Ca2+ Transient in Heart Muscle Cells","volume":"122","author":"Fowler","year":"2018","journal-title":"Circ. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"H564","DOI":"10.1152\/ajpheart.00441.2013","article-title":"Enhanced currents through L-type calcium channels in cardiomyocytes disturb the electrophysiology of the dystrophic heart","volume":"306","author":"Koenig","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1161\/01.RES.79.2.194","article-title":"Ca2+ influx during the cardiac action potential in guinea pig ventricular myocytes","volume":"79","author":"Grantham","year":"1996","journal-title":"Circ. Res."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Brini, M., and Carafoli, E. (2011). The plasma membrane Ca2+ ATPase and the plasma membrane sodium calcium exchanger cooperate in the regulation of cell calcium. Cold Spring Harb. Perspect. Biol., 3.","DOI":"10.1101\/cshperspect.a004168"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Chou, A.C., Ju, Y.T., and Pan, C.Y. (2015). Calmodulin Interacts with the Sodium\/Calcium Exchanger NCX1 to Regulate Activity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138856"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1016\/j.febslet.2014.01.003","article-title":"Gap junction regulation by calmodulin","volume":"588","author":"Zou","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Peracchia, C. (2021). Gap Junction Channelopathies and Calmodulinopathies. Do Disease-Causing Calmodulin Mutants Affect Direct Cell-Cell Communication?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179169"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/j.1471-4159.2009.06436.x","article-title":"CaMKII associates with CaV1.2 L-type calcium channels via selected beta subunits to enhance regulatory phosphorylation","volume":"112","author":"Abiria","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1097\/FJC.0b013e3181a25078","article-title":"Calcium\/calmodulin-dependent kinase II regulation of cardiac ion channels","volume":"54","author":"Bers","year":"2009","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Mustroph, J., Maier, L.S., and Wagner, S. (2014). CaMKII regulation of cardiac K channels. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00020"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.hrthm.2011.01.030","article-title":"Ca2+-calmodulin-dependent protein kinase II regulation of cardiac excitation-transcription coupling","volume":"8","author":"Bers","year":"2011","journal-title":"Heart Rhythm."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Thanassoulas, A., Vassilakopoulou, V., Calver, B.L., Buntwal, L., Smith, A., Lai, C., Kontogianni, I., Livaniou, E., Nounesis, G., and Lai, F.A. (2023). Life-threatening arrhythmogenic CaM mutations disrupt CaM binding to a distinct RyR2 CaM-binding pocket. Biochim. Biophys. Acta Gen. Subj., 1867.","DOI":"10.1016\/j.bbagen.2023.130313"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/hmg\/ddad042","article-title":"Human calmodulin mutations cause arrhythmia and affect neuronal function in C. elegans","volume":"32","author":"Jensen","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e012036","DOI":"10.1161\/CIRCEP.123.012036","article-title":"Single Construct Suppression and Replacement Gene Therapy for the Treatment of All CALM1-, CALM2-, and CALM3-Mediated Arrhythmia Disorders","volume":"17","author":"Hamrick","year":"2024","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"12516","DOI":"10.1074\/jbc.RA118.002728","article-title":"Peptide-based sequestration of the adaptor protein Nck1 in pancreatic beta cells enhances insulin biogenesis and protects against diabetogenic stresses","volume":"293","author":"Kefalas","year":"2018","journal-title":"J. Biol. Chem."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/22\/1763\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:58:06Z","timestamp":1762930686000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/22\/1763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,11]]},"references-count":136,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["cells14221763"],"URL":"https:\/\/doi.org\/10.3390\/cells14221763","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,11]]}}}