ATP promotes development of afterdepolarizations and triggered activity in cardiac myocytes.
The effect of extracellular ATP on transient inward current (Iti), delayed afterdepolarization (DAD), early afterdepolarization (EAD), and triggered activity were investigated in guinea pig isolated ventricular myocytes. ATP alone did not induce afterdepolarizations nor did it significantly alter the resting membrane potentials and action potentials. However, when it was applied with drugs known to increase intracellular Ca2+, ATP facilitated the induction of afterdepolarizations and triggered activity in approximately 60% of the cells. In the presence of isoproterenol, ATP increased the amplitude of Iti and DADs by 55 and 206%, respectively, and caused increases in the amplitude of L-type Ca2+ current (ICa) and EADs, which occasionally led to triggered activity. Similarly, addition of ATP increased the amplitude of Iti and DADs induced by elevated extracellular Ca2+ by 110 and 83%, respectively. Ryanodine inhibited the ATP-induced increase in Iti but not the increase in ICa. In the presence of BAY K 8644 or quinidine, ATP not only further prolonged the action potential durations by 18 +/- 4 and 17 +/- 4%, respectively, but also increased the amplitude of EADs. The present results show a novel arrhythmogenic effect of extracellular ATP, which facilitates the genesis of triggered arrhythmias when Ca2+ influx is increased, probably by further increasing Ca2+ influx from extracellular medium and Ca2+ release from intracellular stores.
Song
Y
Y
Department of Medicine, University of Florida College of Medicine, Gainesville 32610.
Belardinelli
L
L
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*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D004553:Electric Conductivity; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers; D011802:Quinidine / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D013997:Time Factors
D015220:Calcium Channels; D026902:Potassium Channel Blockers; D012433:Ryanodine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000255:Adenosine Triphosphate; D011802:Quinidine; D007545:Isoproterenol; D002118:Calcium