{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T21:55:15Z","timestamp":1788990915563,"version":"build-2803163510"},"reference-count":92,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III CIBERCV","award":["S2022\/BMD-7223"],"award-info":[{"award-number":["S2022\/BMD-7223"]}]},{"name":"Instituto de Salud Carlos III CIBERCV","award":["FPU17\/02731"],"award-info":[{"award-number":["FPU17\/02731"]}]},{"name":"Instituto de Salud Carlos III CIBERCV","award":["BES-2017-080184"],"award-info":[{"award-number":["BES-2017-080184"]}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung and Blood Institute","doi-asserted-by":"publisher","award":["R01HL163943"],"award-info":[{"award-number":["R01HL163943"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung and Blood Institute","doi-asserted-by":"publisher","award":["HR18-00304"],"award-info":[{"award-number":["HR18-00304"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung and Blood Institute","doi-asserted-by":"publisher","award":["LCF\/PR\/HR19\/52160013"],"award-info":[{"award-number":["LCF\/PR\/HR19\/52160013"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung and Blood Institute","doi-asserted-by":"publisher","award":["PI-FIS-2020 # PI20\/01220"],"award-info":[{"award-number":["PI-FIS-2020 # PI20\/01220"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung and Blood Institute","doi-asserted-by":"publisher","award":["PI-FIS-2023 # PI23\/01039"],"award-info":[{"award-number":["PI-FIS-2023 # PI23\/01039"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"Fondo Europeo de Desarrollo Regional","doi-asserted-by":"publisher","award":["PID2020-116935RB-I00"],"award-info":[{"award-number":["PID2020-116935RB-I00"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"Fondo Europeo de Desarrollo Regional","doi-asserted-by":"publisher","award":["BFU2016-75144-R"],"award-info":[{"award-number":["BFU2016-75144-R"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"Fondo Europeo de Desarrollo Regional","doi-asserted-by":"publisher","award":["MCIN\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"Fondo Europeo de Desarrollo Regional","doi-asserted-by":"publisher","award":["736\/C\/2020"],"award-info":[{"award-number":["736\/C\/2020"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"Fondo Europeo de Desarrollo Regional","doi-asserted-by":"publisher","award":["CB16\/11\/00458"],"award-info":[{"award-number":["CB16\/11\/00458"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"Fondo Europeo de Desarrollo Regional","doi-asserted-by":"publisher","award":["CB\/11\/00222"],"award-info":[{"award-number":["CB\/11\/00222"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"Fondo Europeo de Desarrollo Regional","doi-asserted-by":"publisher","award":["GA-965286"],"award-info":[{"award-number":["GA-965286"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"Fondo Europeo de Desarrollo Regional","doi-asserted-by":"publisher","award":["S2022\/BMD7229"],"award-info":[{"award-number":["S2022\/BMD7229"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We investigated the role of Lgi3-4 proteins in cardiac electrophysiology, with a specific focus on IKur, and their potential contribution to the pathophysiology of atrial fibrillation (AF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In human atrial tissue and heterologous cells, Lgi3 and Lgi4 interacted with KV1.5 channels. In a mouse model of AAV9-mediated cardiac-specific Lgi4 expression, sinoatrial and atrioventricular conduction were impaired, resulting in a prolonged QRS interval. Action potential repolarisation was delayed in atrial and ventricular cardiomyocytes from Lgi4 mice. In HEK293 cells, Lgi3-4 impaired KV1.5\/KV\u03b2 association, partially reversing the KV\u03b2-induced inactivation and reducing IKur amplitude. These results correlated with the reduced KV1.5 membrane expression and IKur density observed in Lgi4 cardiomyocytes and HEK293 cells. Notably, Lgi4 protein expression was lower in atrial tissue from patients with AF than in sinus rhythm patients. The reduced Lgi4 protein levels in AF were also associated with an altered colocalisation with KV1.5 channels, suggesting potential disruption in their functional interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We conclude that Lgi3-4 proteins are new components of the cardiac KV1.5 channelosome. They modulate IKur by interfering with the KV1.5-KV\u03b2 interaction. Significantly, Lgi4 is dysregulated differently in paroxysmal vs. permanent AF. The results identify Lgi3-4 proteins as novel regulators of the KV1.5 channelosome, opening new pathways for investigating the role of IKur dysfunction in the mechanism of atrial fibrillation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag049","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:41:26Z","timestamp":1773927686000},"page":"874-891","source":"Crossref","is-referenced-by-count":1,"title":["Lgi3-4 proteins modulate the KV1.5 channelosome and are potential therapeutic targets for atrial fibrillation"],"prefix":"10.1093","volume":"122","author":[{"given":"Paula G","family":"Socu\u00e9llamos","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Sols-Morreale CSIC-UAM , Arturo Duperier, 4, Madrid 28029 ,","place":["Spain"]},{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Melchor Fern\u00e1ndez Almagro, 3, Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Mac\u00edas","sequence":"additional","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Melchor Fern\u00e1ndez Almagro, 3, Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela","family":"de Benito-Bueno","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Sols-Morreale CSIC-UAM , Arturo Duperier, 4, Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco M","family":"Cruz","sequence":"additional","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Melchor Fern\u00e1ndez Almagro, 3, Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Redondo-Moya","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Sols-Morreale CSIC-UAM , Arturo Duperier, 4, Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Coronado","sequence":"additional","affiliation":[{"name":"Institute of Health Research Puerta de Hierro-Segovia de Arana, IDIPHISA , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0785-3826","authenticated-orcid":false,"given":"Elvira","family":"Ramil","sequence":"additional","affiliation":[{"name":"Institute of Health Research Puerta de Hierro-Segovia de Arana, IDIPHISA , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8131-819X","authenticated-orcid":false,"given":"Silvia","family":"Rosado","sequence":"additional","affiliation":[{"name":"Institute of Health Research Puerta de Hierro-Segovia de Arana, IDIPHISA , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa Carolina","family":"Rios-Rosado","sequence":"additional","affiliation":[{"name":"Departamento de Cirug\u00eda Cardiaca, Hospital Universitario Puerta de Hierro , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Valencia-Avezuela","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Sols-Morreale CSIC-UAM , Arturo Duperier, 4, Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Andr\u00e9s-Delgado","sequence":"additional","affiliation":[{"name":"Departamento de Anatom\u00eda, Histolog\u00eda y Neurociencias, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Bl\u00e1zquez","sequence":"additional","affiliation":[{"name":"Departamento de Cirug\u00eda Cardiaca, Hospital Universitario La Paz , Madrid ,","place":["Spain"]},{"name":"\u00c1rea Quir\u00fargica, Complejo Asistencial Universitario de Salamanca , Salamanca ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Forteza-Gil","sequence":"additional","affiliation":[{"name":"Departamento de Cirug\u00eda Cardiaca, Hospital Universitario Puerta de Hierro , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Guti\u00e9rrez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Departamento de Biomim\u00e9ticos, Instituto de Qu\u00edmica M\u00e9dica (IQM-CSIC) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Jalife","sequence":"additional","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Melchor Fern\u00e1ndez Almagro, 3, Madrid 28029 ,","place":["Spain"]},{"name":"Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan , Ann Arbor, MI ,","place":["USA"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3929-1960","authenticated-orcid":false,"given":"Carmen","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Sols-Morreale CSIC-UAM , Arturo Duperier, 4, Madrid 28029 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"2026052213545992500_cvag049-B1","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41569-022-00820-8","article-title":"Epidemiology and modifiable risk factors for atrial fibrillation","volume":"20","author":"Elliott","year":"2023","journal-title":"Nat Rev Cardiol"},{"key":"2026052213545992500_cvag049-B2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/eurheartj\/ehaa612","article-title":"2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European association for cardio-thoracic surgery (EACTS)","volume":"42","author":"Hindricks","year":"2021","journal-title":"Eur Heart J"},{"key":"2026052213545992500_cvag049-B3","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1517\/13543780902762850","article-title":"I Kur\/Kv1.5 channel blockers for the treatment of atrial fibrillation","volume":"18","author":"Tamargo","year":"2009","journal-title":"Expert Opin Investig Drugs"},{"key":"2026052213545992500_cvag049-B4","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1161\/01.RES.73.1.210","article-title":"Identity of a novel delayed rectifier current from human heart with a cloned K+ channel current","volume":"73","author":"Fedida","year":"1993","journal-title":"Circ Res"},{"key":"2026052213545992500_cvag049-B5","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1161\/01.RES.80.6.772","article-title":"Outward Kv current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation","volume":"80","author":"Van Wagoner","year":"1997","journal-title":"Circ Res"},{"key":"2026052213545992500_cvag049-B6","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1093\/eurheartj\/ehs442","article-title":"Genetic variation in KCNA5: impact on the atrial-specific potassium current IKur in patients with lone atrial fibrillation","volume":"34","author":"Christophersen","year":"2013","journal-title":"Eur Heart J"},{"key":"2026052213545992500_cvag049-B7","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1161\/CIRCEP.114.002519","article-title":"Functional characterization of rare variants implicated in susceptibility to lone atrial fibrillation","volume":"8","author":"Hayashi","year":"2015","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2026052213545992500_cvag049-B8","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/S0735-1097(00)01195-5","article-title":"Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels","volume":"37","author":"Brundel","year":"2001","journal-title":"J Am Coll Cardiol"},{"key":"2026052213545992500_cvag049-B9","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1016\/j.jacc.2010.02.028","article-title":"In humans, chronic atrial fibrillation decreases the transient outward current and ultrarapid component of the delayed rectifier current differentially on each atria and increases the slow component of the delayed rectifier current in both","volume":"55","author":"Caballero","year":"2010","journal-title":"J Am Coll Cardiol"},{"key":"2026052213545992500_cvag049-B10","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1124\/pr.117.014183","article-title":"Mechanisms and drug development in atrial fibrillation","volume":"70","author":"Calvo","year":"2018","journal-title":"Pharmacol Rev"},{"key":"2026052213545992500_cvag049-B11","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1139\/cjpp-2017-0024","article-title":"Atrial-selective K + channel blockers: potential antiarrhythmic drugs in atrial fibrillation?","volume":"95","author":"Ravens","year":"2017","journal-title":"Can J Physiol Pharmacol"},{"key":"2026052213545992500_cvag049-B12","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1074\/jbc.271.5.2406","article-title":"Functional differences in Kv1.5 currents expressed in mammalian cell lines are due to the presence of endogenous Kv\u03b22.1 subunits","volume":"271","author":"Uebele","year":"1996","journal-title":"J Biol Chem"},{"key":"2026052213545992500_cvag049-B13","doi-asserted-by":"crossref","first-page":"C1485","DOI":"10.1152\/ajpcell.1998.274.6.C1485","article-title":"Distinct domains of the voltage-gated K+ channel Kv\u03b21.3 \u03b2-subunit affect voltage-dependent gating","volume":"274","author":"Uebele","year":"1998","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026052213545992500_cvag049-B14","doi-asserted-by":"crossref","first-page":"21416","DOI":"10.1074\/jbc.M111.328278","article-title":"Protein kinase C (PKC) activity regulates functional effects of Kv\u03b21.3 subunit on KV1.5 channels","volume":"287","author":"David","year":"2012","journal-title":"J Biol Chem"},{"key":"2026052213545992500_cvag049-B15","doi-asserted-by":"crossref","first-page":"25824","DOI":"10.1074\/jbc.272.41.25824","article-title":"Separable Kv\u03b2 subunit domains Alter expression and gating of potassium channels","volume":"272","author":"Accili","year":"1997","journal-title":"J Biol Chem"},{"key":"2026052213545992500_cvag049-B16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.yjmcc.2019.09.013","article-title":"Metabolic regulation of Kv channels and cardiac repolarization by Kv\u03b22 subunits","volume":"137","author":"Kilfoil","year":"2019","journal-title":"J Mol Cell Cardiol"},{"key":"2026052213545992500_cvag049-B17","doi-asserted-by":"crossref","first-page":"H1851","DOI":"10.1152\/ajpheart.01045.2007","article-title":"The anchoring protein SAP97 retains Kv1.5 channels in the plasma membrane of cardiac myocytes","volume":"294","author":"Abi-Char","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026052213545992500_cvag049-B18","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.hrthm.2014.09.057","article-title":"Cardiac-specific ablation of synapse-associated protein SAP97 in mice decreases potassium currents but not sodium current","volume":"12","author":"Gillet","year":"2015","journal-title":"Heart Rhythm"},{"key":"2026052213545992500_cvag049-B19","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.yjmcc.2005.03.013","article-title":"KChIP2 modulates the cell surface expression of Kv1.5-encoded K channels","volume":"39","author":"Li","year":"2005","journal-title":"J Mol Cell Cardiol"},{"key":"2026052213545992500_cvag049-B20","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1093\/cvr\/cvn038","article-title":"Four and a half LIM protein 1: a partner for KCNA5 in human atrium","volume":"78","author":"Yang","year":"2008","journal-title":"Cardiovasc Res"},{"key":"2026052213545992500_cvag049-B21","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1152\/physrev.00002.2005","article-title":"Molecular physiology of cardiac repolarization","volume":"85","author":"Nerbonne","year":"2005","journal-title":"Physiol Rev"},{"key":"2026052213545992500_cvag049-B22","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0014-5793(02)02713-8","article-title":"The LGI1 gene involved in lateral temporal lobe epilepsy belongs to a new subfamily of leucine-rich repeat proteins","volume":"519","author":"Gu","year":"2002","journal-title":"FEBS Lett"},{"key":"2026052213545992500_cvag049-B23","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1042\/AN20120095","article-title":"LGI proteins in the nervous system","volume":"5","author":"Kegel","year":"2013","journal-title":"ASN Neuro"},{"key":"2026052213545992500_cvag049-B24","doi-asserted-by":"crossref","first-page":"e202211031","DOI":"10.1083\/jcb.202211031","article-title":"LGI3\/2\u2013ADAM23 interactions cluster Kv1 channels in myelinated axons to regulate refractory period","volume":"222","author":"Kozar-Gillan","year":"2023","journal-title":"J Cell Biol"},{"key":"2026052213545992500_cvag049-B25","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1073\/pnas.0914537107","article-title":"Disruption of LGI1\u2013linked synaptic complex causes abnormal synaptic transmission and epilepsy","volume":"107","author":"Fukata","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026052213545992500_cvag049-B26","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.gene.2012.07.016","article-title":"Phylogenetic and molecular evolution of the ADAM (A Disintegrin And Metalloprotease) gene family from Xenopus tropicalis, to Mus musculus, Rattus norvegicus, and Homo sapiens","volume":"507","author":"Long","year":"2012","journal-title":"Gene"},{"key":"2026052213545992500_cvag049-B27","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.neuron.2006.01.033","article-title":"The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kv\u03b21","volume":"49","author":"Schulte","year":"2006","journal-title":"Neuron"},{"key":"2026052213545992500_cvag049-B28","doi-asserted-by":"crossref","first-page":"7719","DOI":"10.1073\/pnas.1618656114","article-title":"LGI1 tunes intrinsic excitability by regulating the density of axonal Kv1 channels","volume":"114","author":"Seagar","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026052213545992500_cvag049-B29","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/j.1471-4159.2011.07605.x","article-title":"Mutant LGI1 inhibits seizure-induced trafficking of Kv4.2 potassium channels","volume":"120","author":"Smith","year":"2012","journal-title":"J Neurochem"},{"key":"2026052213545992500_cvag049-B30","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13578-023-00983-y","article-title":"A patient-derived mutation of epilepsy-linked LGI1 increases seizure susceptibility through regulating Kv1.1","volume":"13","author":"Zhou","year":"2023","journal-title":"Cell Biosci"},{"key":"2026052213545992500_cvag049-B31","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1212\/WNL.0b013e318247ccbf","article-title":"Domain-dependent clustering and genotype-phenotype analysis of LGI1 mutations in ADPEAF","volume":"78","author":"Ho","year":"2012","journal-title":"Neurology"},{"key":"2026052213545992500_cvag049-B32","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/ng832","article-title":"Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features","volume":"30","author":"Kalachikov","year":"2002","journal-title":"Nat Genet"},{"key":"2026052213545992500_cvag049-B33","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1093\/hmg\/11.9.1119","article-title":"Mutations in the LGI1\/epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy","volume":"11","author":"Morante-Redolat","year":"2002","journal-title":"Hum Mol Genet"},{"key":"2026052213545992500_cvag049-B34","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1093\/brain\/awq213","article-title":"Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan\u2019s syndrome and acquired neuromyotonia","volume":"133","author":"Irani","year":"2010","journal-title":"Brain"},{"key":"2026052213545992500_cvag049-B35","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/S1474-4422(10)70137-X","article-title":"Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series","volume":"9","author":"Lai","year":"2010","journal-title":"Lancet Neurol"},{"key":"2026052213545992500_cvag049-B36","doi-asserted-by":"crossref","first-page":"18161","DOI":"10.1523\/JNEUROSCI.3506-13.2013","article-title":"Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1-ADAM22 interaction and reduce synaptic AMPA receptors","volume":"33","author":"Ohkawa","year":"2013","journal-title":"J Neurosci"},{"key":"2026052213545992500_cvag049-B37","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1001\/jamaneurol.2014.1234","article-title":"Episodic bradycardia as neurocardiac prodrome to voltage-gated potassium channel complex\/leucine-rich, glioma inactivated 1 antibody encephalitis","volume":"71","author":"Naasan","year":"2014","journal-title":"JAMA Neurol"},{"key":"2026052213545992500_cvag049-B38","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1016\/j.ajhg.2022.07.006","article-title":"A reverse genetics and genomics approach to gene paralog function and disease: myokymia and the juxtaparanode","volume":"109","author":"Marafi","year":"2022","journal-title":"Am J Hum Genet"},{"key":"2026052213545992500_cvag049-B39","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/nn1598","article-title":"The claw paw mutation reveals a role for Lgi4 in peripheral nerve development","volume":"9","author":"Bermingham","year":"2006","journal-title":"Nat Neurosci"},{"key":"2026052213545992500_cvag049-B40","doi-asserted-by":"crossref","first-page":"3857","DOI":"10.1523\/JNEUROSCI.6287-09.2010","article-title":"Adam22 is a Major neuronal receptor for Lgi4-mediated Schwann cell signaling","volume":"30","author":"Ozkaynak","year":"2010","journal-title":"J Neurosci"},{"key":"2026052213545992500_cvag049-B41","doi-asserted-by":"crossref","first-page":"387","DOI":"10.7150\/ijbs.4.387","article-title":"LGI1 and LGI4 bind to ADAM22, ADAM23 and ADAM11","volume":"4","author":"Sagane","year":"2008","journal-title":"Int J Biol Sci"},{"key":"2026052213545992500_cvag049-B42","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.ajhg.2017.02.006","article-title":"Loss-of-function mutations in LGI4, a secreted ligand involved in Schwann cell myelination, are responsible for arthrogryposis multiplex congenita","volume":"100","author":"Xue","year":"2017","journal-title":"Am J Hum Genet"},{"key":"2026052213545992500_cvag049-B43","doi-asserted-by":"crossref","first-page":"103756","DOI":"10.1016\/j.ejmg.2019.103756","article-title":"A mild phenotype of LGI4-related arthrogryposis multiplex congenita with intrafamilial variability","volume":"63","author":"Mishra","year":"2020","journal-title":"Eur J Med Genet"},{"key":"2026052213545992500_cvag049-B44","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1128\/JVI.72.3.2224-2232.1998","article-title":"Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus","volume":"72","author":"Xiao","year":"1998","journal-title":"J Virol"},{"key":"2026052213545992500_cvag049-B45","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S0076-6879(00)16760-6","article-title":"[48] production and purification of recombinant adeno-associated virus","volume":"316","author":"Hauswirth","year":"2000","journal-title":"Methods Enzymol"},{"key":"2026052213545992500_cvag049-B46","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1016\/j.jacc.2015.01.045","article-title":"Exercise triggers ARVC phenotype in mice expressing a disease-causing mutated version of human plakophilin-2","volume":"65","author":"Cruz","year":"2015","journal-title":"J Am Coll Cardiol"},{"key":"2026052213545992500_cvag049-B47","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1093\/cvr\/cvab055","article-title":"Paclitaxel mitigates structural alterations and cardiac conduction system defects in a mouse model of Hutchinson\u2013Gilford progeria syndrome","volume":"118","author":"Mac\u00edas","year":"2022","journal-title":"Cardiovasc Res"},{"key":"2026052213545992500_cvag049-B48","doi-asserted-by":"crossref","first-page":"9170","DOI":"10.3390\/ijms23169170","article-title":"Modulation of KV4.3-KChIP2 channels by IQM-266: role of DPP6 and KCNE2","volume":"23","author":"De Benito-Bueno","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026052213545992500_cvag049-B49","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1161\/hh1701.095644","article-title":"Gender-based differences in cardiac repolarization in mouse ventricle","volume":"89","author":"Tr\u00e9panier-Boulay","year":"2001","journal-title":"Circ Res"},{"key":"2026052213545992500_cvag049-B50","first-page":"1730","article-title":"Programmed electrical stimulation in mice","author":"Li","year":"2010","journal-title":"J Vis Exp"},{"key":"2026052213545992500_cvag049-B51","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1093\/cvr\/cvs299","article-title":"Early repolarization in mice causes overestimation of ventricular activation time by the QRS duration","volume":"97","author":"Boukens","year":"2013","journal-title":"Cardiovasc Res"},{"key":"2026052213545992500_cvag049-B52","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1146\/annurev.med.47.1.135","article-title":"The cardiac ion channels: relevance to management of arrhythmias","volume":"47","author":"Roden","year":"1996","journal-title":"Annu Rev Med"},{"key":"2026052213545992500_cvag049-B53","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1469-7793.1999.0011o.x","article-title":"Elimination of the transient outward current and action potential prolongation in mouse atrial myocytes expressing a dominant negative Kv4 \u03b1 subunit","volume":"519","author":"Xu","year":"1999","journal-title":"J Physiol"},{"key":"2026052213545992500_cvag049-B54","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1161\/01.RES.78.5.903","article-title":"Adrenergic modulation of ultrarapid delayed rectifier K+ current in human atrial myocytes","volume":"78","author":"Li","year":"1996","journal-title":"Circ Res"},{"key":"2026052213545992500_cvag049-B55","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1111\/j.1469-7793.1998.779bd.x","article-title":"Overexpression of nerve growth factor in the heart alters ion channel activity and beta-adrenergic signalling in an adult transgenic mouse","volume":"512","author":"Heath","year":"1998","journal-title":"J Physiol"},{"key":"2026052213545992500_cvag049-B56","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1093\/cvr\/cvq359","article-title":"Targeting atrioventricular differences in ion channel properties for terminating acute atrial fibrillation in pigs","volume":"89","author":"Pandit","year":"2011","journal-title":"Cardiovasc Res"},{"key":"2026052213545992500_cvag049-B57","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/j.1469-7793.1999.0385v.x","article-title":"Adrenergic control of the ultrarapid delayed rectifier current in canine atrial myocytes","volume":"516","author":"Yue","year":"1999","journal-title":"J Physiol"},{"key":"2026052213545992500_cvag049-B58","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1093\/eurheartj\/ehn140","article-title":"Downregulation of the calcium current in human right atrial myocytes from patients in sinus rhythm but with a high risk of atrial fibrillation","volume":"29","author":"Dinanian","year":"2008","journal-title":"Eur Heart J"},{"key":"2026052213545992500_cvag049-B59","doi-asserted-by":"crossref","first-page":"705","DOI":"10.3389\/fphys.2017.00705","article-title":"Adrenergic stress protection of human iPS cell-derived cardiomyocytes by fast Kv7.1 recycling","volume":"8","author":"Piccini","year":"2017","journal-title":"Front Physiol"},{"key":"2026052213545992500_cvag049-B60","doi-asserted-by":"crossref","first-page":"29612","DOI":"10.1074\/jbc.M704402200","article-title":"Rab-GTPase-dependent endocytic recycling of KV1.5 in atrial myocytes","volume":"282","author":"McEwen","year":"2007","journal-title":"J Biol Chem"},{"key":"2026052213545992500_cvag049-B61","doi-asserted-by":"crossref","first-page":"4914","DOI":"10.1111\/bph.12822","article-title":"PKC inhibition results in a Kv 1.5 + Kv \u03b21.3 pharmacology closer to Kv 1.5 channels: Kv 1.5 + Kv \u03b21.3 pharmacology and PKC","volume":"171","author":"Mac\u00edas","year":"2014","journal-title":"Br J Pharmacol"},{"key":"2026052213545992500_cvag049-B62","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1038\/s41467-017-01747-2","article-title":"Region and cell-type resolved quantitative proteomic map of the human heart","volume":"8","author":"Doll","year":"2017","journal-title":"Nat Commun"},{"key":"2026052213545992500_cvag049-B63","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.pbiomolbio.2007.07.003","article-title":"Characterization of the effects of ryanodine, TTX, E-4031 and 4-AP on the sinoatrial and atrioventricular nodes","volume":"96","author":"Nikmaram","year":"2008","journal-title":"Prog Biophys Mol Biol"},{"key":"2026052213545992500_cvag049-B64","doi-asserted-by":"crossref","first-page":"e000246","DOI":"10.1161\/JAHA.113.000246","article-title":"Functional, anatomical, and molecular investigation of the cardiac conduction system and arrhythmogenic atrioventricular ring tissue in the rat heart","volume":"2","author":"Atkinson","year":"2013","journal-title":"J Am Heart Assoc"},{"key":"2026052213545992500_cvag049-B65","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1177\/002215540004800606","article-title":"Presence of the Kv1.5K(+) channel in the sinoatrial node","volume":"48","author":"Dobrzynski","year":"2000","journal-title":"J Histochem Cytochem"},{"key":"2026052213545992500_cvag049-B66","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1113\/jphysiol.2004.063446","article-title":"Functional properties of K+ currents in adult mouse ventricular myocytes","volume":"559","author":"Brouillette","year":"2004","journal-title":"J Physiol"},{"key":"2026052213545992500_cvag049-B67","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1161\/01.CIR.0000145155.60288.71","article-title":"Role of I \u00a0Kur in controlling action potential shape and contractility in the human atrium: influence of chronic atrial fibrillation","volume":"110","author":"Wettwer","year":"2004","journal-title":"Circulation"},{"key":"2026052213545992500_cvag049-B68","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S0092-8674(01)00588-8","article-title":"A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia","volume":"107","author":"Kuo","year":"2001","journal-title":"Cell"},{"key":"2026052213545992500_cvag049-B69","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.yjmcc.2009.07.013","article-title":"Molecular determinants of cardiac transient outward potassium current (I(to)) expression and regulation","volume":"48","author":"Niwa","year":"2010","journal-title":"J Mol Cell Cardiol"},{"key":"2026052213545992500_cvag049-B70","doi-asserted-by":"crossref","first-page":"H1978","DOI":"10.1152\/ajpheart.01373.2005","article-title":"Differential modulation of Kv4.2 and Kv4.3 channels by calmodulin-dependent protein kinase II in rat cardiac myocytes","volume":"291","author":"Colinas","year":"2006","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026052213545992500_cvag049-B71","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1161\/01.RES.0000156890.25876.63","article-title":"Accessory Kv\u03b2 1 subunits differentially modulate the functional expression of voltage-gated K + channels in mouse ventricular myocytes","volume":"96","author":"Aimond","year":"2005","journal-title":"Circ Res"},{"key":"2026052213545992500_cvag049-B72","doi-asserted-by":"crossref","first-page":"25355","DOI":"10.1074\/jbc.274.36.25355","article-title":"Phosphorylation is required for alteration of Kv1.5K+ channel function by the Kv\u03b21.3 subunit","volume":"274","author":"Kwak","year":"1999","journal-title":"J Biol Chem"},{"key":"2026052213545992500_cvag049-B73","doi-asserted-by":"crossref","first-page":"H71","DOI":"10.1152\/ajpheart.00260.2008","article-title":"Shared requirement for dynein function and intact microtubule cytoskeleton for normal surface expression of cardiac potassium channels","volume":"296","author":"Loewen","year":"2009","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026052213545992500_cvag049-B74","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1124\/mol.107.042093","article-title":"Caveolin regulates Kv1.5 trafficking to cholesterol-rich membrane microdomains","volume":"73","author":"McEwen","year":"2008","journal-title":"Mol Pharmacol"},{"key":"2026052213545992500_cvag049-B75","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1074\/jbc.272.5.3022","article-title":"Potassium channel \u00e4 and \u03b2 subunits assemble in the endoplasmic Reticulum","volume":"272","author":"Nagaya","year":"1997","journal-title":"J Biol Chem"},{"key":"2026052213545992500_cvag049-B76","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/S0896-6273(00)80104-X","article-title":"\u03b2Subunits promote K+ channel surface expression through effects early in biosynthesis","volume":"16","author":"Shi","year":"1996","journal-title":"Neuron"},{"key":"2026052213545992500_cvag049-B77","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.cbi.2017.03.011","article-title":"Heteromeric complexes of aldo-keto reductase auxiliary K V \u03b2 subunits (AKR6A) regulate sarcolemmal localization of K V 1.5 in coronary arterial myocytes","volume":"276","author":"Nystoriak","year":"2017","journal-title":"Chem Biol Interact"},{"key":"2026052213545992500_cvag049-B78","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41421-024-00738-0","article-title":"Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome","volume":"11","author":"Mond\u00e9jar-Parre\u00f1o","year":"2025","journal-title":"Cell Discov"},{"key":"2026052213545992500_cvag049-B79","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1124\/mol.105.011668","article-title":"Structural basis for competition between drug binding and Kv\u03b21.3 accessory subunit-induced N-type inactivation of Kv1.5 channels","volume":"68","author":"Decher","year":"2005","journal-title":"Mol Pharmacol"},{"key":"2026052213545992500_cvag049-B80","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1038\/emboj.2008.231","article-title":"Structural determinants of Kvbeta1.3-induced channel inactivation: a hairpin modulated by PIP2","volume":"27","author":"Decher","year":"2008","journal-title":"EMBO J"},{"key":"2026052213545992500_cvag049-B81","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1126\/science.1129947","article-title":"Epilepsy-related ligand\/receptor complex LGI1 and ADAM22 regulate synaptic transmission","volume":"313","author":"Fukata","year":"2006","journal-title":"Science"},{"key":"2026052213545992500_cvag049-B82","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1523\/JNEUROSCI.4661-09.2010","article-title":"ADAM22, a Kv1 channel-interacting protein, recruits membrane-associated guanylate kinases to juxtaparanodes of myelinated axons","volume":"30","author":"Ogawa","year":"2010","journal-title":"J Neurosci"},{"key":"2026052213545992500_cvag049-B83","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/415219a","article-title":"New ideas about atrial fibrillation 50 years on","volume":"415","author":"Nattel","year":"2002","journal-title":"Nature"},{"key":"2026052213545992500_cvag049-B84","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1161\/01.CIR.96.11.4027","article-title":"Functional mechanisms underlying tachycardia-induced sustained atrial fibrillation in a chronic dog model","volume":"96","author":"Gaspo","year":"1997","journal-title":"Circulation"},{"key":"2026052213545992500_cvag049-B85","doi-asserted-by":"crossref","first-page":"377","DOI":"10.3904\/kjim.2010.25.4.377","article-title":"Remodeling of ion channel expression in patients with chronic atrial fibrillation and mitral valvular heart disease","volume":"25","author":"Oh","year":"2010","journal-title":"Korean J Intern Med"},{"key":"2026052213545992500_cvag049-B86","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/j.1540-8167.2000.tb00024.x","article-title":"Molecular remodeling of Kv4.3 potassium channels in human atrial fibrillation","volume":"11","author":"Grammer","year":"2000","journal-title":"J Cardiovasc Electrophysiol"},{"key":"2026052213545992500_cvag049-B87","doi-asserted-by":"crossref","first-page":"106684","DOI":"10.1016\/j.phrs.2023.106684","article-title":"Sigma-1 receptor modulation fine-tunes KV1.5 channels and impacts pulmonary vascular function","volume":"189","author":"Vera-Zambrano","year":"2023","journal-title":"Pharmacol Res"},{"key":"2026052213545992500_cvag049-B88","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1186\/s12864-017-3683-9","article-title":"Reduced changes in protein compared to mRNA levels across non-proliferating tissues","volume":"18","author":"Perl","year":"2017","journal-title":"BMC Genomics"},{"key":"2026052213545992500_cvag049-B89","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.hrthm.2015.10.003","article-title":"The positive frequency-dependent electrophysiological effects of the IKur inhibitor XEN-D0103 are desirable for the treatment of atrial fibrillation","volume":"13","author":"Ford","year":"2016","journal-title":"Heart Rhythm"},{"key":"2026052213545992500_cvag049-B90","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fphar.2014.00026","article-title":"Effects of IKur blocker MK-0448 on human right atrial action potentials from patients in sinus rhythm and in permanent atrial fibrillation","volume":"5","author":"Loose","year":"2014","journal-title":"Front Pharmacol"},{"key":"2026052213545992500_cvag049-B91","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s42826-021-00102-3","article-title":"A comparative review on heart ion channels, action potentials and electrocardiogram in rodents and human: extrapolation of experimental insights to clinic","volume":"37","author":"Joukar","year":"2021","journal-title":"Lab Anim Res"},{"key":"2026052213545992500_cvag049-B92","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1152\/physrev.00007.2016","article-title":"Murine electrophysiological models of cardiac arrhythmogenesis","volume":"97","author":"Huang","year":"2017","journal-title":"Physiol Rev"}],"container-title":["Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cardiovascres\/advance-article-pdf\/doi\/10.1093\/cvr\/cvag049\/67412288\/cvag049.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/122\/7\/874\/67412288\/cvag049.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/122\/7\/874\/67412288\/cvag049.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T17:55:16Z","timestamp":1779472516000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article\/122\/7\/874\/8528998"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,19]]},"references-count":92,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,3,19]]},"published-print":{"date-parts":[[2026,5,22]]}},"URL":"https:\/\/doi.org\/10.1093\/cvr\/cvag049","relation":{},"ISSN":["0008-6363","1755-3245"],"issn-type":[{"value":"0008-6363","type":"print"},{"value":"1755-3245","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,3,19]]}}}