{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:04:44Z","timestamp":1789650284965,"version":"4.0.0"},"reference-count":51,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004869","name":"University of M\u00fcnster Medical School","doi-asserted-by":"publisher","award":["ST121119"],"award-info":[{"award-number":["ST121119"]}],"id":[{"id":"10.13039\/501100004869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004869","name":"University of M\u00fcnster Medical School","doi-asserted-by":"publisher","award":["19CVD03"],"award-info":[{"award-number":["19CVD03"]}],"id":[{"id":"10.13039\/501100004869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004869","name":"University of M\u00fcnster Medical School","doi-asserted-by":"publisher","award":["DE1482\/9-1"],"award-info":[{"award-number":["DE1482\/9-1"]}],"id":[{"id":"10.13039\/501100004869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004869","name":"University of M\u00fcnster Medical School","doi-asserted-by":"publisher","award":["35722"],"award-info":[{"award-number":["35722"]}],"id":[{"id":"10.13039\/501100004869","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondation Leducq Paris","award":["ST121119"],"award-info":[{"award-number":["ST121119"]}]},{"name":"Fondation Leducq Paris","award":["19CVD03"],"award-info":[{"award-number":["19CVD03"]}]},{"name":"Fondation Leducq Paris","award":["DE1482\/9-1"],"award-info":[{"award-number":["DE1482\/9-1"]}]},{"name":"Fondation Leducq Paris","award":["35722"],"award-info":[{"award-number":["35722"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ST121119"],"award-info":[{"award-number":["ST121119"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["19CVD03"],"award-info":[{"award-number":["19CVD03"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DE1482\/9-1"],"award-info":[{"award-number":["DE1482\/9-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["35722"],"award-info":[{"award-number":["35722"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Austrian Science Fund","award":["ST121119"],"award-info":[{"award-number":["ST121119"]}]},{"name":"Austrian Science Fund","award":["19CVD03"],"award-info":[{"award-number":["19CVD03"]}]},{"name":"Austrian Science Fund","award":["DE1482\/9-1"],"award-info":[{"award-number":["DE1482\/9-1"]}]},{"name":"Austrian Science Fund","award":["35722"],"award-info":[{"award-number":["35722"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cav1.3 voltage-gated L-type calcium channels (LTCCs) are involved in cardiac pacemaking, hearing and hormone secretion, but are also expressed postsynaptically in neurons. So far, homozygous loss of function mutations in CACNA1D encoding the Cav1.3 \u03b11-subunit are described in congenital sinus node dysfunction and deafness. In addition, germline mutations in CACNA1D have been linked to neurodevelopmental syndromes including epileptic seizures, autism, intellectual disability and primary hyperaldosteronism. Here, a three-generation family with a syndromal phenotype of sinus node dysfunction, idiopathic epilepsy and attention deficit hyperactivity disorder (ADHD) is investigated. Whole genome sequencing and functional heterologous expression studies were used to identify the disease-causing mechanisms in this novel syndromal disorder. We identified a heterozygous non-synonymous variant (p.Arg930His) in the CACNA1D gene that cosegregated with the combined clinical phenotype in an autosomal dominant manner. Functional heterologous expression studies showed that the CACNA1D variant induces isoform-specific alterations of Cav1.3 channel gating: a gain of ion channel function was observed in the brain-specific short CACNA1D isoform (Cav1.3S), whereas a loss of ion channel function was seen in the long (Cav1.3L) isoform. The combined gain-of-function (GOF) and loss-of-function (LOF) induced by the R930H variant are likely to be associated with the rare combined clinical and syndromal phenotypes in the family. The GOF in the Cav1.3S variant with high neuronal expression is likely to result in epilepsy, whereas the LOF in the long Cav1.3L variant results in sinus node dysfunction.<\/jats:p>","DOI":"10.3390\/ijms232214215","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T03:12:20Z","timestamp":1668654740000},"page":"14215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Whole Exome Sequencing Identifies a Heterozygous Variant in the Cav1.3 Gene CACNA1D Associated with Familial Sinus Node Dysfunction and Focal Idiopathic Epilepsy"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2326-7069","authenticated-orcid":false,"given":"Susanne","family":"Rinn\u00e9","sequence":"first","affiliation":[{"name":"Institute of Physiology and Pathophysiology, Vegetative Physiology, University of Marburg, 35037 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Stallmeyer","sequence":"additional","affiliation":[{"name":"Institute for Genetics of Heart Diseases (IfGH), University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Pinggera","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Center for Molecular Biosciences, University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Netter","sequence":"additional","affiliation":[{"name":"Institute of Physiology and Pathophysiology, Vegetative Physiology, University of Marburg, 35037 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina A.","family":"Matschke","sequence":"additional","affiliation":[{"name":"Institute of Physiology and Pathophysiology, Vegetative Physiology, University of Marburg, 35037 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5829-3676","authenticated-orcid":false,"given":"Sven","family":"Dittmann","sequence":"additional","affiliation":[{"name":"Institute for Genetics of Heart Diseases (IfGH), University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Kirchhefer","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Neudorf","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Kinder-und Jugendmedizin, Klinik f\u00fcr Kinderheilkunde III-Bereich Kardiologie, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0558-217X","authenticated-orcid":false,"given":"Joachim","family":"Opp","sequence":"additional","affiliation":[{"name":"Ev. Krankenhaus Oberhausen, 46047 Oberhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9406-7120","authenticated-orcid":false,"given":"J\u00f6rg","family":"Striessnig","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Center for Molecular Biosciences, University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9433-687X","authenticated-orcid":false,"given":"Niels","family":"Decher","sequence":"additional","affiliation":[{"name":"Institute of Physiology and Pathophysiology, Vegetative Physiology, University of Marburg, 35037 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-2501","authenticated-orcid":false,"given":"Eric","family":"Schulze-Bahr","sequence":"additional","affiliation":[{"name":"Institute for Genetics of Heart Diseases (IfGH), University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1172\/JCI200316387","article-title":"Pacemaker channel dysfunction in a patient with sinus node disease","volume":"111","author":"Neu","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1172\/JCI200318062","article-title":"Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A)","volume":"112","author":"Benson","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e002238","DOI":"10.1161\/CIRCGEN.118.002238","article-title":"Familial Sinus Node Disease Caused by a Gain of GIRK (G-Protein Activated Inwardly Rectifying K(+) Channel) Channel Function","volume":"12","author":"Kuss","year":"2019","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1161\/CIRCULATIONAHA.118.036761","article-title":"Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation","volume":"139","author":"Yamada","year":"2019","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1172\/JCI38292","article-title":"Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I","volume":"119","author":"Kruse","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/humu.21599","article-title":"Mutational spectrum in the Ca2+\u2014Activated cation channel gene TRPM4 in patients with cardiac conductance disturbances","volume":"33","author":"Stallmeyer","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1161\/CIRCRESAHA.116.310112","article-title":"A Mutation in the G-Protein Gene GNB2 Causes Familial Sinus Node and Atrioventricular Conduction Dysfunction","volume":"120","author":"Stallmeyer","year":"2017","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.ajhg.2016.08.011","article-title":"GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability","volume":"99","author":"Lodder","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"dmm037994","DOI":"10.1242\/dmm.037994","article-title":"Genetic variation in GNB5 causes bradycardia by augmenting the cholinergic response via increased acetylcholine-activated potassium current (IK,ACh)","volume":"12","author":"Veerman","year":"2019","journal-title":"Dis. Model. Mech."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1161\/01.CIR.22.5.887","article-title":"Congenital familial nodal rhythm","volume":"22","author":"Bacos","year":"1960","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.hrthm.2017.01.020","article-title":"Sick sinus syndrome with HCN4 mutations shows early onset and frequent association with atrial fibrillation and left ventricular noncompaction","volume":"14","author":"Ishikawa","year":"2017","journal-title":"Heart Rhythm"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nn.2694","article-title":"Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness","volume":"14","author":"Baig","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5830","DOI":"10.1046\/j.1432-1327.2000.01670.x","article-title":"G-protein mediated gating of inward-rectifier K+ channels","volume":"267","author":"Mark","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1113\/JP273259","article-title":"Computational analysis of the human sinus node action potential: Model development and effects of mutations","volume":"595","author":"Fabbri","year":"2017","journal-title":"J. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s00424-020-02421-1","article-title":"Channelopathies of voltage-gated L-type Cav1.3\/alpha1D and T-type Cav3.1\/alpha1G Ca2+ channels in dysfunction of heart automaticity","volume":"472","author":"Torrente","year":"2020","journal-title":"Pflugers Arch."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5543","DOI":"10.1073\/pnas.0935295100","article-title":"Functional role of L-type Cav1.3 Ca2+ channels in cardiac pacemaker activity","volume":"100","author":"Mangoni","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"22100","DOI":"10.1074\/jbc.M101469200","article-title":"alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages","volume":"276","author":"Koschak","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.neuroscience.2010.02.037","article-title":"Voltage-activated calcium channel expression profiles in mouse brain and cultured hippocampal neurons","volume":"167","author":"Schlick","year":"2010","journal-title":"Neuroscience"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3389\/fncel.2015.00309","article-title":"Cell-type-specific tuning of Cav1.3 Ca2+-channels by a C-terminal automodulatory domain","volume":"9","author":"Scharinger","year":"2015","journal-title":"Front. Cell Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"42736","DOI":"10.1074\/jbc.M111.269951","article-title":"Functional properties of a newly identified C-terminal splice variant of Cav1.3 L-type Ca2+ channels","volume":"286","author":"Bock","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0092-8674(00)00013-1","article-title":"Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels","volume":"102","author":"Platzer","year":"2000","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/s10038-018-0542-8","article-title":"Identification of CACNA1D variants associated with sinoatrial node dysfunction and deafness in additional Pakistani families reveals a clinical significance","volume":"64","author":"Liaqat","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13229-019-0310-4","article-title":"Biophysical classification of a CACNA1D de novo mutation as a high-risk mutation for a severe neurodevelopmental disorder","volume":"11","author":"Hofer","year":"2020","journal-title":"Mol. Autism"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.biopsych.2014.11.020","article-title":"CACNA1D de novo mutations in autism spectrum disorders activate Cav1.3 L-type calcium channels","volume":"77","author":"Pinggera","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1093\/hmg\/ddx175","article-title":"New gain-of-function mutation shows CACNA1D as recurrently mutated gene in autism spectrum disorders and epilepsy","volume":"26","author":"Pinggera","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/ng.2695","article-title":"Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism","volume":"45","author":"Scholl","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s10038-018-0549-1","article-title":"Exome sequencing identifies a novel nonsense mutation of Ring Finger Protein 207 in a Chinese family with Long QT syndrome and syncope","volume":"64","author":"Fan","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"D1039","DOI":"10.1093\/nar\/gkx1039","article-title":"VarCards: An integrated genetic and clinical database for coding variants in the human genome","volume":"46","author":"Li","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: Predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"Rentzsch","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"42725","DOI":"10.1074\/jbc.M111.265207","article-title":"Functional characterization of alternative splicing in the C terminus of L-type CaV1.3 channels","volume":"286","author":"Tan","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1469-7793.2001.0093k.x","article-title":"Determinants of activation kinetics in mammalian hyperpolarization-activated cation channels","volume":"537","author":"Ishii","year":"2001","journal-title":"J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fnmol.2017.00016","article-title":"The First Extracellular Linker Is Important for Several Aspects of the Gating Mechanism of Human TRPA1 Channel","volume":"10","author":"Marsakova","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4823","DOI":"10.1074\/jbc.M510197200","article-title":"A molecular determinant of nickel inhibition in Cav3.2 T-type calcium channels","volume":"281","author":"Kang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.1074\/jbc.M109.067660","article-title":"Structural determinants of the high affinity extracellular zinc binding site on Cav3.2 T-type calcium channels","volume":"285","author":"Kang","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1085\/jgp.201110699","article-title":"Molecular and biophysical basis of glutamate and trace metal modulation of voltage-gated Cav2.3 calcium channels","volume":"139","author":"Shcheglovitov","year":"2012","journal-title":"J. Gen. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/nrn1671","article-title":"The neurobiology of zinc in health and disease","volume":"6","author":"Frederickson","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14444","DOI":"10.1074\/jbc.RA118.003681","article-title":"Role of a conserved glutamine in the function of voltage-gated Ca(2+) channels revealed by a mutation in human CACNA1D","volume":"293","author":"Lopez","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3389\/fneur.2019.00505","article-title":"The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children","volume":"10","author":"Long","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"49","DOI":"10.17116\/jnevro201811812149","article-title":"[The third case report a patient with primary aldosteronism, seizures, and neurologic abnormalities (PASNA) syndrome de novo variant mutations in the CACNA1D gene]","volume":"118","author":"Semenova","year":"2018","journal-title":"Zhurnal Nevrol. I Psikhiatrii Im. SS Korsakova"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/gim.2017.76","article-title":"Genomic diagnostics within a medically underserved population: Efficacy and implications","volume":"20","author":"Strauss","year":"2018","journal-title":"Genet. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/pedi.12512","article-title":"A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia","volume":"18","author":"Flanagan","year":"2017","journal-title":"Pediatr. Diabetes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s004390050516","article-title":"The long QT syndrome: A novel missense mutation in the S6 region of the KVLQT1 gene","volume":"100","author":"Wilde","year":"1997","journal-title":"Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/ng0297-186","article-title":"A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome","volume":"15","author":"Neyroud","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s00424-020-02418-w","article-title":"De novo CACNA1D Ca2+ channelopathies: Clinical phenotypes and molecular mechanism","volume":"472","author":"Ortner","year":"2020","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Louradour, J., Bortolotti, O., Torre, E., Bidaud, I., Lamb, N., Fernandez, A., Le Guennec, J.Y., Mangoni, M.E., and Mesirca, P. (2022). L-Type Cav1.3 calcium channels are required for beta-adrenergic triggered automaticity in dormant mouse sinoatrial pacemaker cells. Cells, 11.","DOI":"10.3390\/cells11071114"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1074\/mcp.M113.035600","article-title":"Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics","volume":"13","author":"Fagerberg","year":"2014","journal-title":"Mol. Cell Proteom."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/GIM.0b013e31816b5cae","article-title":"ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007","volume":"10","author":"Richards","year":"2008","journal-title":"Genet. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/j.bpj.2014.02.017","article-title":"C-terminal modulatory domain controls coupling of voltage-sensing to pore opening in Cav1.3 L-type Ca2+ channels","volume":"106","author":"Lieb","year":"2014","journal-title":"Biophys. J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14215\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:20:00Z","timestamp":1760145600000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,17]]},"references-count":51,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232214215"],"URL":"https:\/\/doi.org\/10.3390\/ijms232214215","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,17]]}}}