A model for early afterdepolarizations: induction with the Ca2+ channel agonist Bay K 8644
- PMID: 2449297
- DOI: 10.1161/01.res.62.3.563
A model for early afterdepolarizations: induction with the Ca2+ channel agonist Bay K 8644
Abstract
Early afterdepolarizations (EADs) are one mechanism proposed to cause certain cardiac arrhythmias. We studied the effect of the Ca2+ channel agonist Bay K 8644 (1 x 10(-8) to 5 x 10(-5) M) on normally polarized sheep and canine cardiac Purkinje fiber short segments. EADs occurred with higher Bay K 8644 concentrations and had an average take-off potential of -34 mV. The initiation of EADs was preceded by lengthening of action potential duration and flattening of the plateau. Induction of EADs with Bay K 8644 was enhanced by low stimulation frequencies, lowering of [K]o, addition of tetraethylammonium chloride, or application of depolarizing constant current pulses during the plateau. EADs were abolished by increasing stimulation frequency, raising [K]o, the addition of tetrodotoxin, lidocaine, ethmozin, verapamil, and nitrendipine, or application of repolarizing constant current pulses. Using current pulses to modify the action potential plateau, a steep inverse relationship was found between the EAD peak voltage and its take-off potential, and EADs could be initiated over only a narrow range of take-off potentials. Thus, interventions that suppressed EADs shortened action potential duration or shifted the plateau away from the voltage range needed to initiate EADs. These observations suggest that mechanisms dependent on both time and voltage underlie EADs, and provide a unifying hypothesis for the induction of the EADs. We propose that induction of EADs requires 1) lengthening of action potential duration within a plateau voltage range where 2) recovery from inactivation and reactivation of an inward current possibly carried through Ca2+ channels can occur.
Similar articles
-
Early afterdepolarizations in cardiac myocytes: beyond reduced repolarization reserve.Cardiovasc Res. 2013 Jul 1;99(1):6-15. doi: 10.1093/cvr/cvt104. Epub 2013 Apr 25. Cardiovasc Res. 2013. PMID: 23619423 Free PMC article. Review.
-
Early afterdepolarizations produced by d,l-sotalol and clofilium.J Cardiovasc Electrophysiol. 1997 Jun;8(6):667-78. doi: 10.1111/j.1540-8167.1997.tb01830.x. J Cardiovasc Electrophysiol. 1997. PMID: 9209968
-
Early after/depolarizations and triggered activity: mechanisms and autonomic regulation.Fundam Clin Pharmacol. 1993;7(1):39-49. doi: 10.1111/j.1472-8206.1993.tb00216.x. Fundam Clin Pharmacol. 1993. PMID: 8458601 Review.
-
[Asymmetrical changes in electrical activity of Purkinje fibers and muscle cells after administration of BAY K 8644. A new model of cardiac arrhythmia].Biull Vsesoiuznogo Kardiol Nauchn Tsentra AMN SSSR. 1989;12(1):6-11. Biull Vsesoiuznogo Kardiol Nauchn Tsentra AMN SSSR. 1989. PMID: 2472820 Russian.
-
Early afterdepolarizations: mechanism of induction and block. A role for L-type Ca2+ current.Circ Res. 1989 May;64(5):977-90. doi: 10.1161/01.res.64.5.977. Circ Res. 1989. PMID: 2468430
Cited by
-
Dissecting the roles of calcium cycling and its coupling with voltage in the genesis of early afterdepolarizations in cardiac myocyte models.PLoS Comput Biol. 2024 Feb 28;20(2):e1011930. doi: 10.1371/journal.pcbi.1011930. eCollection 2024 Feb. PLoS Comput Biol. 2024. PMID: 38416778 Free PMC article.
-
Long QT syndrome-associated calmodulin variants disrupt the activity of the slowly activating delayed rectifier potassium channel.J Physiol. 2023 Sep;601(17):3739-3764. doi: 10.1113/JP284994. Epub 2023 Jul 10. J Physiol. 2023. PMID: 37428651 Free PMC article.
-
Bifurcations to transient and oscillatory excitations in inhomogeneous excitable media: Insights into arrhythmogenesis in long QT syndrome.Phys Rev E. 2023 Mar;107(3-1):034402. doi: 10.1103/PhysRevE.107.034402. Phys Rev E. 2023. PMID: 37073009 Free PMC article.
-
Discussion on Repolarization Reserve between Patients with Coronary Heart Disease and Normal Controls.Comput Math Methods Med. 2022 Aug 18;2022:7944969. doi: 10.1155/2022/7944969. eCollection 2022. Comput Math Methods Med. 2022. PMID: 36035296 Free PMC article.
-
Bifurcations and Proarrhythmic Behaviors in Cardiac Electrical Excitations.Biomolecules. 2022 Mar 16;12(3):459. doi: 10.3390/biom12030459. Biomolecules. 2022. PMID: 35327651 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous