Cytosolic calcium changes affect the incidence of early afterdepolarizations in canine ventricular myocytes.
This study was designed to investigate the influence of cytosolic Ca(2+) levels ([Ca(2+)]i) on action potential duration (APD) and on the incidence of early afterdepolarizations (EADs) in canine ventricular cardiomyocytes. Action potentials (AP) of isolated cells were recorded using conventional sharp microelectrodes, and the concomitant [Ca(2+)]i was monitored with the fluorescent dye Fura-2. EADs were evoked at a 0.2 Hz pacing rate by inhibiting the rapid delayed rectifier K(+) current with dofetilide, by activating the late sodium current with veratridine, or by activating the L-type calcium current with BAY K8644. These interventions progressively prolonged the AP and resulted in initiation of EADs. Reducing [Ca(2+)]i by application of the cell-permeant Ca(2+) chelator BAPTA-AM lengthened the AP at 1.0 Hz if it was applied alone, in the presence of veratridine, or in the presence of BAY K8644. However, BAPTA-AM shortened the AP if the cells were pretreated with dofetilide. The incidence of the evoked EADs was strongly reduced by BAPTA-AM in dofetilide, moderately reduced in veratridine, whereas EAD incidence was increased by BAPTA-AM in the presence of BAY K8644. Based on these experimental data, changes in [Ca(2+)]i have marked effects on APD as well as on the incidence of EADs; however, the underlying mechanisms may be different, depending on the mechanism of EAD generation. As a consequence, reduction of [Ca(2+)]i may eliminate EADs under some, but not all, experimental conditions.
a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, Nagyerdei krt 98, Hungary.|b Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary.
Balázs
B
Horváth
a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, Nagyerdei krt 98, Hungary.
Bence
B
Hegyi
a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, Nagyerdei krt 98, Hungary.
Kornél
K
Kistamás
a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, Nagyerdei krt 98, Hungary.
Krisztina
K
Váczi
a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, Nagyerdei krt 98, Hungary.
Tamás
T
Bányász
a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, Nagyerdei krt 98, Hungary.|c Division of Sport Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
János
J
Magyar
a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, Nagyerdei krt 98, Hungary.|d Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Hungary.
Norbert
N
Szentandrássy
a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, Nagyerdei krt 98, Hungary.|d Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Hungary.
Péter P
PP
Nánási
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D065096:Calcium Chelating Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014701:Veratridine / Q000494:pharmacology
D002120:Calcium Channel Agonists; D065096:Calcium Chelating Agents; D010627:Phenethylamines; D013449:Sulfonamides; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D014701:Veratridine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C063533:dofetilide; D002118:Calcium
Ca2+ chelators; action potential duration; arrhythmogenesis; arythmogenèse; canine myocytes; chélateurs de l’ion Ca2+; concentration intracellulaire de l’ion Ca2+; durée du potentiel d’action; early afterdepolarizations; electrophysiology; fluorescent Ca2+ indicator dyes; indicateurs fluorescents de l’ion Ca2+; intracellular Ca2+ levels; myocytes canins; postdépolarisations précoces; électrophysiologie