title: Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm.
abstract: 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.
  
  
  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.
authors.affiliation: Division of Cardiovascular Medicine, Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Marianna
authors.initials: M
authors.lastname: Meo
authors.affiliation: Laboratoire d'Informatique, Signaux et Systèmes de Sophia Antipolis (I3S), Université Nice Sophia Antipolis, CNRS, Nice, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Meste
authors.affiliation: Division of Cardiovascular Medicine, Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Signore
authors.affiliation: Division of Cardiovascular Medicine, Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sorrentino
authors.affiliation: Division of Cardiovascular Medicine, Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cannata
authors.affiliation: Division of Cardiovascular Medicine, Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Division of Cardiovascular Medicine, Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Fondazione Cardiocentro Ticino, University of Zurich, Lugano, Switzerland.
authors.forename: Alex
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: Division of Cardiovascular Medicine, Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Marco
authors.initials: M
authors.lastname: Luciani
authors.affiliation: Division of Cardiovascular Medicine, Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Kannappan
authors.affiliation: Division of Cardiovascular Medicine, Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Polina
authors.initials: P
authors.lastname: Goichberg
authors.affiliation: Division of Cardiovascular Medicine, Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Fondazione Cardiocentro Ticino, University of Zurich, Lugano, Switzerland.
authors.forename: Annarosa
authors.initials: A
authors.lastname: Leri
authors.affiliation: Division of Cardiovascular Medicine, Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Fondazione Cardiocentro Ticino, University of Zurich, Lugano, Switzerland.
authors.forename: Piero
authors.initials: P
authors.lastname: Anversa
authors.affiliation: Division of Cardiovascular Medicine, Departments of Anesthesia and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Department of Physiology, New York Medical College, Valhalla, NY marcello_rota@nymc.edu.
authors.forename: Marcello
authors.initials: M
authors.lastname: Rota
mesh_terms: D000200:Action Potentials; D000465:Algorithms; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications*; D058065:Diabetic Cardiomyopathies / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate; D007700:Kinetics; D008297:Male; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D012815:Signal Processing, Computer-Assisted
chemical_list: D001786:Blood Glucose; D015221:Potassium Channels; D011188:Potassium
keywords: diabetes; electrophysiology; repolarization; variability