title: Contribution of ion currents to beat-to-beat variability of action potential duration in canine ventricular myocytes.
abstract: Although beat-to-beat variability (short-term variability, SV) of action potential duration (APD) is considered as a predictor of imminent cardiac arrhythmias, the underlying mechanisms are still not clear. In the present study, therefore, we aimed to determine the role of the major cardiac ion currents, APD, stimulation frequency, and changes in the intracellular Ca(2+) concentration ([Ca(2+)]i) on the magnitude of SV. Action potentials were recorded from isolated canine ventricular cardiomyocytes using conventional microelectrode techniques. SV was an exponential function of APD, when APD was modified by current injections. Drug effects were characterized as relative SV changes by comparing the drug-induced changes in SV to those in APD according to the exponential function obtained with current pulses. Relative SV was increased by dofetilide, HMR 1556, nisoldipine, and veratridine, while it was reduced by BAY K8644, tetrodotoxin, lidocaine, and isoproterenol. Relative SV was also increased by increasing the stimulation frequency and [Ca(2+)]i. In summary, relative SV is decreased by ion currents involved in the negative feedback regulation of APD (I Ca, I Ks, and I Kr), while it is increased by I Na and I to. We conclude that drug-induced effects on SV should be evaluated in relation with the concomitant changes in APD. Since relative SV was decreased by ion currents playing critical role in the negative feedback regulation of APD, blockade of these currents, or the beta-adrenergic pathway, may carry also some additional proarrhythmic risk in addition to their well-known antiarrhythmic action.
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary.|Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.
authors: Norbert
authors: N
authors: Szentandrássy
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary.
authors: Kornél
authors: K
authors: Kistamás
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary.
authors: Bence
authors: B
authors: Hegyi
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary.
authors: Balázs
authors: B
authors: Horváth
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary.
authors: Ferenc
authors: F
authors: Ruzsnavszky
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary.
authors: Krisztina
authors: K
authors: Váczi
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary.|Division of Sport Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: János
authors: J
authors: Magyar
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary.
authors: Tamás
authors: T
authors: Bányász
authors: Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
authors: András
authors: A
authors: Varró
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary. nanasi.peter@med.unideb.hu.|Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary. nanasi.peter@med.unideb.hu.
authors: Péter P
authors: PP
authors: Nánási
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004285:Dogs; D025461:Feedback, Physiological; D005260:Female; D006352:Heart Ventricles / Q000166:cytology*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017136:Ion Transport; D007545:Isoproterenol / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015737:Nisoldipine / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D002839:Chromans; C420023:HMR 1556; D007473:Ion Channels; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D013449:Sulfonamides; D013779:Tetrodotoxin; D015737:Nisoldipine; D014701:Veratridine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D008012:Lidocaine; D007545:Isoproterenol; C063533:dofetilide; D002118:Calcium