{"id":"https://openalex.org/W4416368014","doi":"https://doi.org/10.1371/journal.pcbi.1013616","title":"Biphasic effects on human atrial arrhythmogenicity of L-type calcium channel mutations associated with a Brugada/Short QT overlap syndrome - insights from a multiscale simulation study","display_name":"Biphasic effects on human atrial arrhythmogenicity of L-type calcium channel mutations associated with a Brugada/Short QT overlap syndrome - insights from a multiscale simulation study","publication_year":2025,"publication_date":"2025-11-19","ids":{"openalex":"https://openalex.org/W4416368014","doi":"https://doi.org/10.1371/journal.pcbi.1013616","pmid":"https://pubmed.ncbi.nlm.nih.gov/41259367"},"language":"en","primary_location":{"id":"doi:10.1371/journal.pcbi.1013616","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1013616","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1013616&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1013616&type=printable","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Yirong Xiang","orcid":"https://orcid.org/0000-0001-6887-5610"},"institutions":[{"id":"https://openalex.org/I28407311","display_name":"University of Manchester","ror":"https://ror.org/027m9bs27","country_code":"GB","type":"education","lineage":["https://openalex.org/I28407311"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Yirong Xiang","raw_affiliation_strings":["Biological Physics Group, Department of Physics and Astronomy, The University of Manchester, Manchester, United Kingdom"],"raw_orcid":"https://orcid.org/0000-0001-6887-5610","affiliations":[{"raw_affiliation_string":"Biological Physics Group, Department of Physics and Astronomy, The University of Manchester, Manchester, United Kingdom","institution_ids":["https://openalex.org/I28407311"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5037737415","display_name":"Jules C. Hancox","orcid":"https://orcid.org/0000-0002-2055-6482"},"institutions":[{"id":"https://openalex.org/I28407311","display_name":"University of Manchester","ror":"https://ror.org/027m9bs27","country_code":"GB","type":"education","lineage":["https://openalex.org/I28407311"]},{"id":"https://openalex.org/I36234482","display_name":"University of Bristol","ror":"https://ror.org/0524sp257","country_code":"GB","type":"education","lineage":["https://openalex.org/I36234482"]},{"id":"https://openalex.org/I4210139332","display_name":"Bristol Laboratories (United Kingdom)","ror":"https://ror.org/03bm3h723","country_code":"GB","type":"company","lineage":["https://openalex.org/I4210139332"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Jules C. Hancox","raw_affiliation_strings":["Biological Physics Group, Department of Physics and Astronomy, The University of Manchester, Manchester, United Kingdom","Cardiovascular Research Laboratories, Bristol Medical School (THS), Biomedical Sciences Building, University Walk, Bristol, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biological Physics Group, Department of Physics and Astronomy, The University of Manchester, Manchester, United Kingdom","institution_ids":["https://openalex.org/I28407311"]},{"raw_affiliation_string":"Cardiovascular Research Laboratories, Bristol Medical School (THS), Biomedical Sciences Building, University Walk, Bristol, United Kingdom","institution_ids":["https://openalex.org/I36234482","https://openalex.org/I4210139332"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5043271142","display_name":"Henggui Zhang","orcid":"https://orcid.org/0000-0002-0863-5807"},"institutions":[{"id":"https://openalex.org/I28407311","display_name":"University of Manchester","ror":"https://ror.org/027m9bs27","country_code":"GB","type":"education","lineage":["https://openalex.org/I28407311"]},{"id":"https://openalex.org/I3017480383","display_name":"Southwest Medical University","ror":"https://ror.org/00g2rqs52","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I3017480383"]},{"id":"https://openalex.org/I4387154005","display_name":"State Key Laboratory of Digital Medical Engineering","ror":"https://ror.org/03ab0at74","country_code":"CN","type":"facility","lineage":["https://openalex.org/I4387154005","https://openalex.org/I76569877"]},{"id":"https://openalex.org/I76569877","display_name":"Southeast University","ror":"https://ror.org/04ct4d772","country_code":"CN","type":"education","lineage":["https://openalex.org/I76569877"]}],"countries":["CN","GB"],"is_corresponding":true,"raw_author_name":"Henggui Zhang","raw_affiliation_strings":["Biological Physics Group, Department of Physics and Astronomy, The University of Manchester, Manchester, United Kingdom","Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China","State Key Laboratory of Digital Medical Engineering, School of Instrument Science and Engineering, Southeast University, Nanjing, China"],"raw_orcid":"https://orcid.org/0000-0002-0863-5807","affiliations":[{"raw_affiliation_string":"Biological Physics Group, Department of Physics and Astronomy, The University of Manchester, Manchester, United Kingdom","institution_ids":["https://openalex.org/I28407311"]},{"raw_affiliation_string":"Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China","institution_ids":["https://openalex.org/I3017480383"]},{"raw_affiliation_string":"State Key Laboratory of Digital Medical Engineering, School of Instrument Science and Engineering, Southeast University, Nanjing, China","institution_ids":["https://openalex.org/I4387154005","https://openalex.org/I76569877"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":6,"corresponding_author_ids":["https://openalex.org/A5043271142"],"corresponding_institution_ids":["https://openalex.org/I28407311","https://openalex.org/I3017480383","https://openalex.org/I4387154005","https://openalex.org/I76569877"],"apc_list":{"value":2655,"currency":"USD","value_usd":2655},"apc_paid":{"value":2655,"currency":"USD","value_usd":2655},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.43309351,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"21","issue":"11","first_page":"e1013616","last_page":"e1013616"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10217","display_name":"Cardiac electrophysiology and arrhythmias","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10217","display_name":"Cardiac electrophysiology and arrhythmias","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11217","display_name":"Cardiac Arrhythmias and Treatments","score":0.0007999999797903001,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10493","display_name":"Ion channel regulation and function","score":0.0005000000237487257,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/atrial-action-potential","display_name":"Atrial action potential","score":0.7696999907493591},{"id":"https://openalex.org/keywords/atrial-fibrillation","display_name":"Atrial fibrillation","score":0.7006000280380249},{"id":"https://openalex.org/keywords/repolarization","display_name":"Repolarization","score":0.539900004863739},{"id":"https://openalex.org/keywords/brugada-syndrome","display_name":"Brugada syndrome","score":0.5254999995231628},{"id":"https://openalex.org/keywords/electrophysiology","display_name":"Electrophysiology","score":0.4697999954223633},{"id":"https://openalex.org/keywords/missense-mutation","display_name":"Missense mutation","score":0.4578999876976013},{"id":"https://openalex.org/keywords/effective-refractory-period","display_name":"Effective refractory period","score":0.4535999894142151},{"id":"https://openalex.org/keywords/long-qt-syndrome","display_name":"Long QT syndrome","score":0.4431000053882599},{"id":"https://openalex.org/keywords/atrium","display_name":"Atrium (architecture)","score":0.4408000111579895},{"id":"https://openalex.org/keywords/cardiac-arrhythmia","display_name":"Cardiac arrhythmia","score":0.41690000891685486}],"concepts":[{"id":"https://openalex.org/C87520248","wikidata":"https://www.wikidata.org/wiki/Q4817540","display_name":"Atrial action potential","level":4,"score":0.7696999907493591},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.7365999817848206},{"id":"https://openalex.org/C2779161974","wikidata":"https://www.wikidata.org/wiki/Q815819","display_name":"Atrial fibrillation","level":2,"score":0.7006000280380249},{"id":"https://openalex.org/C164705383","wikidata":"https://www.wikidata.org/wiki/Q10379","display_name":"Cardiology","level":1,"score":0.6650000214576721},{"id":"https://openalex.org/C146403970","wikidata":"https://www.wikidata.org/wiki/Q205729","display_name":"Repolarization","level":3,"score":0.539900004863739},{"id":"https://openalex.org/C2777382798","wikidata":"https://www.wikidata.org/wiki/Q599683","display_name":"Brugada syndrome","level":2,"score":0.5254999995231628},{"id":"https://openalex.org/C185263204","wikidata":"https://www.wikidata.org/wiki/Q1154774","display_name":"Electrophysiology","level":2,"score":0.4697999954223633},{"id":"https://openalex.org/C75563809","wikidata":"https://www.wikidata.org/wiki/Q2656896","display_name":"Missense mutation","level":4,"score":0.4578999876976013},{"id":"https://openalex.org/C189327125","wikidata":"https://www.wikidata.org/wiki/Q5347276","display_name":"Effective refractory period","level":3,"score":0.4535999894142151},{"id":"https://openalex.org/C2779703243","wikidata":"https://www.wikidata.org/wiki/Q653924","display_name":"Long QT syndrome","level":3,"score":0.4431000053882599},{"id":"https://openalex.org/C114021368","wikidata":"https://www.wikidata.org/wiki/Q189265","display_name":"Atrium (architecture)","level":3,"score":0.4408000111579895},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4341000020503998},{"id":"https://openalex.org/C2988455589","wikidata":"https://www.wikidata.org/wiki/Q189331","display_name":"Cardiac arrhythmia","level":3,"score":0.41690000891685486},{"id":"https://openalex.org/C104397207","wikidata":"https://www.wikidata.org/wiki/Q72711","display_name":"Electrical conduction system of the heart","level":3,"score":0.40639999508857727},{"id":"https://openalex.org/C2780040984","wikidata":"https://www.wikidata.org/wiki/Q79785","display_name":"Electrocardiography","level":2,"score":0.36039999127388},{"id":"https://openalex.org/C179253579","wikidata":"https://www.wikidata.org/wiki/Q6276958","display_name":"Nerve conduction velocity","level":2,"score":0.3573000133037567},{"id":"https://openalex.org/C70616116","wikidata":"https://www.wikidata.org/wiki/Q1736732","display_name":"Refractory period","level":2,"score":0.3562999963760376},{"id":"https://openalex.org/C519063684","wikidata":"https://www.wikidata.org/wiki/Q706","display_name":"Calcium","level":2,"score":0.3447999954223633},{"id":"https://openalex.org/C113217602","wikidata":"https://www.wikidata.org/wiki/Q416781","display_name":"Ryanodine receptor","level":3,"score":0.3224000036716461},{"id":"https://openalex.org/C111335779","wikidata":"https://www.wikidata.org/wiki/Q3454686","display_name":"Reduction (mathematics)","level":2,"score":0.3192000091075897},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3147999942302704},{"id":"https://openalex.org/C3018640507","wikidata":"https://www.wikidata.org/wiki/Q10334846","display_name":"Atrial myocytes","level":3,"score":0.31439998745918274},{"id":"https://openalex.org/C61381695","wikidata":"https://www.wikidata.org/wiki/Q3302130","display_name":"Cardiac electrophysiology","level":3,"score":0.30720001459121704},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.30169999599456787},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.28519999980926514},{"id":"https://openalex.org/C2777953023","wikidata":"https://www.wikidata.org/wiki/Q1073121","display_name":"Heart rate","level":3,"score":0.28110000491142273},{"id":"https://openalex.org/C111773187","wikidata":"https://www.wikidata.org/wiki/Q1969239","display_name":"QRS complex","level":2,"score":0.2797999978065491},{"id":"https://openalex.org/C28289500","wikidata":"https://www.wikidata.org/wiki/Q7098868","display_name":"Optical mapping","level":2,"score":0.2793000042438507},{"id":"https://openalex.org/C118441451","wikidata":"https://www.wikidata.org/wiki/Q12074763","display_name":"QT interval","level":2,"score":0.2702000141143799},{"id":"https://openalex.org/C18699975","wikidata":"https://www.wikidata.org/wiki/Q14905735","display_name":"Voltage-dependent calcium channel","level":3,"score":0.2667999863624573},{"id":"https://openalex.org/C85520022","wikidata":"https://www.wikidata.org/wiki/Q15322916","display_name":"Calcium channel","level":3,"score":0.2637999951839447},{"id":"https://openalex.org/C2780074459","wikidata":"https://www.wikidata.org/wiki/Q389735","display_name":"Heart disease","level":2,"score":0.2624000012874603},{"id":"https://openalex.org/C2780283014","wikidata":"https://www.wikidata.org/wiki/Q209583","display_name":"Tachycardia","level":2,"score":0.26080000400543213},{"id":"https://openalex.org/C2777008848","wikidata":"https://www.wikidata.org/wiki/Q7246836","display_name":"Proarrhythmia","level":3,"score":0.25929999351501465},{"id":"https://openalex.org/C2909456097","wikidata":"https://www.wikidata.org/wiki/Q189331","display_name":"Conduction abnormalities","level":2,"score":0.2547000050544739},{"id":"https://openalex.org/C2778198053","wikidata":"https://www.wikidata.org/wiki/Q181754","display_name":"Heart failure","level":2,"score":0.2500999867916107}],"mesh":[{"descriptor_ui":"D000200","descriptor_name":"Action Potentials","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000200","descriptor_name":"Action Potentials","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000200","descriptor_name":"Action Potentials","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000200","descriptor_name":"Action Potentials","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001145","descriptor_name":"Arrhythmias, Cardiac","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D001145","descriptor_name":"Arrhythmias, Cardiac","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D001145","descriptor_name":"Arrhythmias, Cardiac","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D001145","descriptor_name":"Arrhythmias, Cardiac","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D001145","descriptor_name":"Arrhythmias, Cardiac","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D001145","descriptor_name":"Arrhythmias, Cardiac","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D001145","descriptor_name":"Arrhythmias, Cardiac","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D001145","descriptor_name":"Arrhythmias, Cardiac","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D001281","descriptor_name":"Atrial Fibrillation","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D001281","descriptor_name":"Atrial Fibrillation","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D001281","descriptor_name":"Atrial Fibrillation","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D001281","descriptor_name":"Atrial Fibrillation","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D001281","descriptor_name":"Atrial Fibrillation","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":false},{"descriptor_ui":"D001281","descriptor_name":"Atrial Fibrillation","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":false},{"descriptor_ui":"D001281","descriptor_name":"Atrial Fibrillation","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":false},{"descriptor_ui":"D001281","descriptor_name":"Atrial Fibrillation","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":false},{"descriptor_ui":"D003198","descriptor_name":"Computer Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003198","descriptor_name":"Computer Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003198","descriptor_name":"Computer Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003198","descriptor_name":"Computer Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006325","descriptor_name":"Heart Atria","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":false},{"descriptor_ui":"D006325","descriptor_name":"Heart Atria","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":false},{"descriptor_ui":"D006325","descriptor_name":"Heart Atria","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":false},{"descriptor_ui":"D006325","descriptor_name":"Heart Atria","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008955","descriptor_name":"Models, Cardiovascular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008955","descriptor_name":"Models, Cardiovascular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008955","descriptor_name":"Models, Cardiovascular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008955","descriptor_name":"Models, Cardiovascular","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013576","descriptor_name":"Syndactyly","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D013576","descriptor_name":"Syndactyly","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D013576","descriptor_name":"Syndactyly","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D013576","descriptor_name":"Syndactyly","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D013576","descriptor_name":"Syndactyly","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D013576","descriptor_name":"Syndactyly","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D013576","descriptor_name":"Syndactyly","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D013576","descriptor_name":"Syndactyly","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020125","descriptor_name":"Mutation, Missense","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020125","descriptor_name":"Mutation, Missense","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020125","descriptor_name":"Mutation, Missense","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020125","descriptor_name":"Mutation, Missense","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020746","descriptor_name":"Calcium Channels, L-Type","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D020746","descriptor_name":"Calcium Channels, L-Type","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D020746","descriptor_name":"Calcium Channels, L-Type","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D020746","descriptor_name":"Calcium Channels, L-Type","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D053840","descriptor_name":"Brugada Syndrome","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D053840","descriptor_name":"Brugada Syndrome","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D053840","descriptor_name":"Brugada Syndrome","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D053840","descriptor_name":"Brugada Syndrome","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D053840","descriptor_name":"Brugada Syndrome","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D053840","descriptor_name":"Brugada Syndrome","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D053840","descriptor_name":"Brugada Syndrome","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D053840","descriptor_name":"Brugada Syndrome","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true}],"locations_count":4,"locations":[{"id":"doi:10.1371/journal.pcbi.1013616","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1013616","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1013616&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},{"id":"pmid:41259367","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41259367","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLoS computational biology","raw_type":null},{"id":"pmh:oai:doaj.org/article:d43f52a41911424aa740ed3097f92981","is_oa":true,"landing_page_url":"https://doaj.org/article/d43f52a41911424aa740ed3097f92981","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"PLoS Computational Biology, Vol 21, Iss 11, p e1013616 (2025)","raw_type":"article"},{"id":"pmh:oai:europepmc.org:11437369","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12629484","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1371/journal.pcbi.1013616","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1013616","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1013616&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},"sustainable_development_goals":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4416368014.pdf","grobid_xml":"https://content.openalex.org/works/W4416368014.grobid-xml"},"referenced_works_count":65,"referenced_works":["https://openalex.org/W66428373","https://openalex.org/W1482350832","https://openalex.org/W1572161927","https://openalex.org/W1754996786","https://openalex.org/W1965633790","https://openalex.org/W1966872591","https://openalex.org/W1976291152","https://openalex.org/W1979003439","https://openalex.org/W1985718987","https://openalex.org/W1992467460","https://openalex.org/W1995182859","https://openalex.org/W2003013939","https://openalex.org/W2004277174","https://openalex.org/W2005591721","https://openalex.org/W2018256150","https://openalex.org/W2019028325","https://openalex.org/W2029750615","https://openalex.org/W2039686430","https://openalex.org/W2045548568","https://openalex.org/W2047456609","https://openalex.org/W2054590326","https://openalex.org/W2056878931","https://openalex.org/W2067313061","https://openalex.org/W2078242986","https://openalex.org/W2080553677","https://openalex.org/W2083828684","https://openalex.org/W2089861793","https://openalex.org/W2091776886","https://openalex.org/W2098963973","https://openalex.org/W2101009102","https://openalex.org/W2107658445","https://openalex.org/W2112520390","https://openalex.org/W2120263248","https://openalex.org/W2120836228","https://openalex.org/W2126899523","https://openalex.org/W2129393568","https://openalex.org/W2130445053","https://openalex.org/W2134877852","https://openalex.org/W2138773108","https://openalex.org/W2139891426","https://openalex.org/W2147836600","https://openalex.org/W2149099209","https://openalex.org/W2154806697","https://openalex.org/W2158133158","https://openalex.org/W2161424604","https://openalex.org/W2161539268","https://openalex.org/W2165168573","https://openalex.org/W2175689245","https://openalex.org/W2289337326","https://openalex.org/W2318517467","https://openalex.org/W2523688192","https://openalex.org/W2531345437","https://openalex.org/W2625476692","https://openalex.org/W2627089767","https://openalex.org/W2743028295","https://openalex.org/W2758962074","https://openalex.org/W2762285869","https://openalex.org/W2770486024","https://openalex.org/W2807010560","https://openalex.org/W2960881087","https://openalex.org/W4214490439","https://openalex.org/W4281939352","https://openalex.org/W4288068074","https://openalex.org/W4293217392","https://openalex.org/W4367601315"],"related_works":[],"abstract_inverted_index":{"Patients":[0],"with":[1,40,46,125],"abbreviated":[2],"cardiac":[3,10],"repolarization":[4],"are":[5],"at":[6,186,193],"increased":[7,191,218,240],"risk":[8],"of":[9,27,53,64,75,80,87,93,164,176,225,243,252,265,268],"arrhythmias":[11],"including":[12],"ventricular":[13],"and":[14,34,69,99,106,121,129,143,155,208,223],"atrial":[15,55,97,114,119,147,177,182,226,273],"fibrillation":[16],"(AF).":[17],"In":[18,255],"this":[19,257],"computational":[20,51],"simulation":[21],"study,":[22],"we":[23],"investigated":[24,102],"pro-arrhythmic":[25],"effects":[26,202,236,267],"loss-of-function":[28,269],"missense":[29],"mutations":[30,71,145,271],"in":[31,38,203,216],"CACNA1C":[32,66,141],"(A39V":[33],"G490R":[35,70,144],"Cav1.2)":[36],"identified":[37],"patients":[39],"a":[41,112,116,231],"phenotype":[42],"combining":[43],"Brugada":[44],"syndrome":[45],"shorter-than-normal":[47],"QT":[48],"intervals.":[49],"Biophysically-detailed":[50],"models":[52,109],"human":[54,123],"cells":[56],"were":[57,90,101],"modified":[58],"to":[59,150,221,238,249],"incorporate":[60],"the":[61,65,73,76,140,162,168,174,253],"functional":[62],"impact":[63],"encoded":[67],"A39V":[68,142],"on":[72,96,272],"reduction":[74,89,215,233],"maximal":[77],"conductance":[78],"(gCaL)":[79],"L-type":[81],"calcium":[82],"channels":[83],"(LTCC).":[84],"Varying":[85],"levels":[86],"gCaL":[88,172],"considered.":[91],"Effects":[92],"deficient":[94],"LTCC":[95,137,270],"excitation":[98,178,228,245],"propagation":[100],"by":[103],"using":[104],"cellular":[105],"multi-dimensional":[107],"tissue":[108,169,211,219],"that":[110,135,247],"included":[111],"one-dimensional":[113],"strand,":[115],"two-dimensional":[117],"idealized":[118],"sheet":[120],"three-dimensional":[122],"atria":[124],"realistic":[126],"anatomical":[127],"structure":[128],"detailed":[130],"electrophysiology.":[131],"Our":[132],"results":[133],"showed":[134,199,234],"reduced":[136],"activity":[138],"from":[139],"accelerated":[146],"repolarization,":[148],"leading":[149],"shortened":[151,173],"action":[152],"potential":[153],"duration":[154],"effective":[156],"refractory":[157],"period,":[158],"as":[159,161],"well":[160],"loss":[163],"their":[165],"rate-dependence.":[166],"At":[167],"level,":[170],"decreased":[171],"wavelength":[175],"waves,":[179,229],"slowed":[180],"down":[181],"conduction":[183],"velocity":[184],"(CV)":[185],"low":[187],"pacing":[188,195],"rates":[189],"but":[190],"it":[192],"high":[194],"rates.":[196],"It":[197],"also":[198],"bi-phasic":[200],"arrhythmogenic":[201],"One-dimensional":[204],"(1D),":[205],"Two-dimensional":[206],"(2D)":[207],"Three-dimensional":[209],"(3D)":[210],"simulations.":[212],"A":[213],"large":[214],"ICaL":[217],"susceptibility":[220],"initiation":[222],"maintenance":[224],"re-entrant":[227,244],"while":[230],"moderate":[232],"anti-arrhythmic":[235],"due":[237],"an":[239],"meandering":[241],"area":[242],"waves":[246],"led":[248],"early":[250],"self-termination":[251],"reentry.":[254],"conclusion,":[256],"study":[258],"provides":[259],"new":[260],"mechanistic":[261],"insights":[262],"into":[263],"understanding":[264],"biphasic":[266],"pro-arrhythmias.":[274]},"counts_by_year":[],"updated_date":"2026-07-31T08:31:51.225901","created_date":"2025-11-19T00:00:00"}
