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Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm

BACKGROUND: Diabetes is associated with prolongation of the QT interval of the electrocardiogram and enhanced dispersion of ventricular repolarization, factors that, together with atherosclerosis and myocardial ischemia, may promote the occurrence of electrical disorders. Thus, we tested the possibi...

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Autores principales: Meo, Marianna, Meste, Olivier, Signore, Sergio, Sorrentino, Andrea, Cannata, Antonio, Zhou, Yu, Matsuda, Alex, Luciani, Marco, Kannappan, Ramaswamy, Goichberg, Polina, Leri, Annarosa, Anversa, Piero, Rota, Marcello
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802457/
https://www.ncbi.nlm.nih.gov/pubmed/26896476
http://dx.doi.org/10.1161/JAHA.115.003078
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author Meo, Marianna
Meste, Olivier
Signore, Sergio
Sorrentino, Andrea
Cannata, Antonio
Zhou, Yu
Matsuda, Alex
Luciani, Marco
Kannappan, Ramaswamy
Goichberg, Polina
Leri, Annarosa
Anversa, Piero
Rota, Marcello
author_facet Meo, Marianna
Meste, Olivier
Signore, Sergio
Sorrentino, Andrea
Cannata, Antonio
Zhou, Yu
Matsuda, Alex
Luciani, Marco
Kannappan, Ramaswamy
Goichberg, Polina
Leri, Annarosa
Anversa, Piero
Rota, Marcello
author_sort Meo, Marianna
collection PubMed
description BACKGROUND: Diabetes is associated with prolongation of the QT interval of the electrocardiogram and enhanced dispersion of ventricular repolarization, factors that, together with atherosclerosis and myocardial ischemia, may promote the occurrence of electrical disorders. Thus, we tested the possibility that alterations in transmembrane ionic currents reduce the repolarization reserve of myocytes, leading to action potential (AP) prolongation and enhanced beat‐to‐beat variability of repolarization. METHODS AND RESULTS: Diabetes was induced in mice with streptozotocin (STZ), and effects of hyperglycemia on electrical properties of whole heart and myocytes were studied with respect to an untreated control group (Ctrl) using electrocardiographic recordings in vivo, ex vivo perfused hearts, and single‐cell patch‐clamp analysis. Additionally, a newly developed algorithm was introduced to obtain detailed information of the impact of high glucose on AP profile. Compared to Ctrl, hyperglycemia in STZ‐treated animals was coupled with prolongation of the QT interval, enhanced temporal dispersion of electrical recovery, and susceptibility to ventricular arrhythmias, defects observed, in part, in the Akita mutant mouse model of type I diabetes. AP was prolonged and beat‐to‐beat variability of repolarization was enhanced in diabetic myocytes, with respect to Ctrl cells. Density of Kv K(+) and L‐type Ca(2+) currents were decreased in STZ myocytes, in comparison to cells from normoglycemic mice. Pharmacological reduction of Kv currents in Ctrl cells lengthened AP duration and increased temporal dispersion of repolarization, reiterating features identified in diabetic myocytes. CONCLUSIONS: Reductions in the repolarizing K(+) currents may contribute to electrical disturbances of the diabetic heart.
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spelling pubmed-48024572016-04-08 Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm Meo, Marianna Meste, Olivier Signore, Sergio Sorrentino, Andrea Cannata, Antonio Zhou, Yu Matsuda, Alex Luciani, Marco Kannappan, Ramaswamy Goichberg, Polina Leri, Annarosa Anversa, Piero Rota, Marcello J Am Heart Assoc Original Research BACKGROUND: Diabetes is associated with prolongation of the QT interval of the electrocardiogram and enhanced dispersion of ventricular repolarization, factors that, together with atherosclerosis and myocardial ischemia, may promote the occurrence of electrical disorders. Thus, we tested the possibility that alterations in transmembrane ionic currents reduce the repolarization reserve of myocytes, leading to action potential (AP) prolongation and enhanced beat‐to‐beat variability of repolarization. METHODS AND RESULTS: Diabetes was induced in mice with streptozotocin (STZ), and effects of hyperglycemia on electrical properties of whole heart and myocytes were studied with respect to an untreated control group (Ctrl) using electrocardiographic recordings in vivo, ex vivo perfused hearts, and single‐cell patch‐clamp analysis. Additionally, a newly developed algorithm was introduced to obtain detailed information of the impact of high glucose on AP profile. Compared to Ctrl, hyperglycemia in STZ‐treated animals was coupled with prolongation of the QT interval, enhanced temporal dispersion of electrical recovery, and susceptibility to ventricular arrhythmias, defects observed, in part, in the Akita mutant mouse model of type I diabetes. AP was prolonged and beat‐to‐beat variability of repolarization was enhanced in diabetic myocytes, with respect to Ctrl cells. Density of Kv K(+) and L‐type Ca(2+) currents were decreased in STZ myocytes, in comparison to cells from normoglycemic mice. Pharmacological reduction of Kv currents in Ctrl cells lengthened AP duration and increased temporal dispersion of repolarization, reiterating features identified in diabetic myocytes. CONCLUSIONS: Reductions in the repolarizing K(+) currents may contribute to electrical disturbances of the diabetic heart. John Wiley and Sons Inc. 2016-02-19 /pmc/articles/PMC4802457/ /pubmed/26896476 http://dx.doi.org/10.1161/JAHA.115.003078 Text en © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Meo, Marianna
Meste, Olivier
Signore, Sergio
Sorrentino, Andrea
Cannata, Antonio
Zhou, Yu
Matsuda, Alex
Luciani, Marco
Kannappan, Ramaswamy
Goichberg, Polina
Leri, Annarosa
Anversa, Piero
Rota, Marcello
Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm
title Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm
title_full Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm
title_fullStr Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm
title_full_unstemmed Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm
title_short Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm
title_sort reduction in kv current enhances the temporal dispersion of the action potential in diabetic myocytes: insights from a novel repolarization algorithm
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802457/
https://www.ncbi.nlm.nih.gov/pubmed/26896476
http://dx.doi.org/10.1161/JAHA.115.003078
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