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dc.contributor.author
Malagueta Vieira, Layse
dc.contributor.author
Fernandez Ruocco, Maria Julieta
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dc.contributor.author
Hortigón Vinagre, María P.
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Zamora, Víctor
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Zayas Arrabal, Julián
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Echeazarra, Leyre
dc.contributor.author
Smith, Godfrey L.
dc.contributor.author
Vila Petroff, Martin Gerarde
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dc.contributor.author
Medei, Emiliano
dc.contributor.author
Casis, Óscar
dc.contributor.author
Gallego, Mónica
dc.date.available
2024-07-08T13:22:24Z
dc.date.issued
2022-05
dc.identifier.citation
Malagueta Vieira, Layse; Fernandez Ruocco, Maria Julieta; Hortigón Vinagre, María P.; Zamora, Víctor; Zayas Arrabal, Julián; et al.; Metformin Reduces Potassium Currents and Prolongs Repolarization in Non-Diabetic Heart; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 23; 11; 5-2022; 1-14
dc.identifier.issn
1422-0067
dc.identifier.uri
http://hdl.handle.net/11336/239337
dc.description.abstract
Metformin is the first choice drug for the treatment of type 2 diabetes due to positive results in reducing hyperglycaemia and insulin resistance. However, diabetic patients have higher risk of ventricular arrhythmia and sudden cardiac death, and metformin failed to reduce ventricular arrhythmia in clinical trials. In order to explore the mechanisms responsible for the lack of protective effect, we investigated in vivo the effect of metformin on cardiac electrical activity in non-diabetic rats; and in vitro in isolated ventricular myocytes, HEK293 cells expressing the hERG channel and human induced pluripotent stem cells derived cardiomyocytes (hIPS-CMs). Surface electrocardiograms showed that long-term metformin treatment (7 weeks) at therapeutic doses prolonged cardiac repolarization, reflected as QT and QTc interval duration, and increased ventricular arrhythmia during the caffeine/dobutamine challenge. Patch-clamp recordings in ventricular myocytes isolated from treated animals showed that the cellular mechanism is a reduction in the cardiac transient outward potassium current (Ito). In vitro, incubation with metformin for 24 h also reduced Ito, prolonged action potential duration, and increased spontaneous contractions in ventricular myocytes isolated from control rats. Metformin incubation also reduced IhERG in HEK293 cells. Finally, metformin incubation prolonged action potential duration at 30% and 90% of repolarization in hIPS-CMs, which is compatible with the reduction of Ito and IhERG. Our results show that metformin directly modifies the electrical behavior of the normal heart. The mechanism consists in the inhibition of repolarizing currents and the subsequent decrease in repolarization capacity, which prolongs AP and QTc duration.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Molecular Diversity Preservation International
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
cardiac action potential
dc.subject
cardiac electrophysiology
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ventricular arrhythmia
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diabetes
dc.subject.classification
Fisiología
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Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Metformin Reduces Potassium Currents and Prolongs Repolarization in Non-Diabetic Heart
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-07-05T11:46:30Z
dc.journal.volume
23
dc.journal.number
11
dc.journal.pagination
1-14
dc.journal.pais
Suiza
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dc.journal.ciudad
Basel
dc.description.fil
Fil: Malagueta Vieira, Layse. Universidad del País Vasco; España
dc.description.fil
Fil: Fernandez Ruocco, Maria Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
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Fil: Hortigón Vinagre, María P.. University of Glasgow; Reino Unido
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Fil: Zamora, Víctor. University of Glasgow; Reino Unido
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Fil: Zayas Arrabal, Julián. Universidad del País Vasco; España
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Fil: Echeazarra, Leyre. Universidad del País Vasco; España
dc.description.fil
Fil: Smith, Godfrey L.. University of Glasgow; Reino Unido
dc.description.fil
Fil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
dc.description.fil
Fil: Medei, Emiliano. Universidade Federal do Rio de Janeiro; Brasil
dc.description.fil
Fil: Casis, Óscar. Universidad del País Vasco; España
dc.description.fil
Fil: Gallego, Mónica. Universidad del País Vasco; España
dc.journal.title
International Journal of Molecular Sciences
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/23/11/6021
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3390/ijms23116021
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