Contributions of Ion Channel Currents to Ventricular Action Potential Changes and Induction of Early Afterdepolarizations During Acute Hypoxia

N. Gaur, Y. Rudy, Livia Hool

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Rationale: Variability in delivery of oxygen can lead to electric instability in the myocardium and the generation of arrhythmias. In addition ischemic heart disease and angina are associated with an increase in circulating catecholamines that further increases the risk of developing ventricular tachyarrhythmias. Objective: We investigated the net effects of acute hypoxia and catecholamines on the cardiac action potential. Methods and Results: We incorporated all published data on the effects of hypoxia on the late Na+ current (INa-L), the fast Na+ current (INa), the basal L-type Ca2+ channel current (ICa-L), and the slow (IKs) and rapid components of the delayed rectifier K+-current (IKr) in the absence and presence of β-adrenergic receptor (β-AR) stimulation into the Luo–Rudy model of the action potential. Hypoxia alone had little effect on the action potential configuration or action potential duration. However in the presence of β-AR stimulation, hypoxia caused a prolongation of the action potential and early afterdepolarizations (EADs) and spontaneous tachycardia were induced. Experiments performed in guinea pig ventricular myocytes confirmed the modeling results. Conclusions: EADs occur predominantly because of the increased sensitivity of ICa-L to β-AR stimulation during hypoxia. β-AR stimulation is necessary to induce EADs as EADs are never observed during hypoxia in the absence of β-AR stimulation.
Original languageEnglish
Pages (from-to)1196-1203
JournalCirculation Research
Volume105
Issue number12
DOIs
Publication statusPublished - 2009

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