ArticleCardiovascular research2012
Role of the transient outward potassium current in the genesis of early afterdepolarizations in cardiac cells.
Article in Cardiovascular research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 68 citations in OpenAlex.
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- Arrhythmias from the Right Ventricular Moderator Band: Diagnosis and Management.Arrhythmia & electrophysiology review · 2020Review
- Big endothelin-1 as a clinical marker for ventricular tachyarrhythmias in patients with post-infarction left ventricular aneurysm.Anatolian journal of cardiology · 2019Article
- Determinants of early afterdepolarization properties in ventricular myocyte models.PLoS computational biology · 2018Article
- Transient Outward KCirculation. Arrhythmia and electrophysiology · 2018Article
- Mitochondrial CaJournal of the American Heart Association · 2018Article
- Cardiac action potential repolarization revisited: early repolarization shows all-or-none behaviour.The Journal of physiology · 2017Review
- Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
aimsThe transient outward potassium current (I(to)) plays important roles in action potential (AP) morphology and dynamics; however, its role in the genesis of early afterdepolarizations (EADs) is not well understood. We aimed to study the effects and mechanisms of I(to) on EAD genesis in cardiac cells using combined experimental and computational approaches. METHODS AND
resultsWe first carried out patch-clamp experiments in isolated rabbit ventricular myocytes exposed to H(2)O(2) (0.2 or 1 mM), in which EADs were induced at a slow pacing rate. EADs were eliminated by either increasing the pacing rate or blocking I(to) with 2 mM 4-aminopyridine. In addition to enhancing the L-type calcium current (I(Ca,L)) and the late sodium current, H(2)O(2) also increased the conductance, slowed inactivation, and accelerated recovery from the inactivation of I(to). Computer simulations showed that I(to) promoted EADs under the condition of reduced repolarization reserve, consistent with the experimental observations. However, EADs were only promoted in the intermediate ranges of the I(to) conductance and the inactivation time constant. The underlying mechanism is that I(to) lowers the AP plateau voltage into the range at which the time-dependent potassium current (namely I(Ks)) activation is further slowed and I(Ca,L) is available for reactivation, leading to voltage oscillations to manifest EADs. Further experimental studies in cardiac cells of other species validated the theoretical predictions.
conclusionIn cardiac cells, I(to), with a proper conductance and inactivation speed, potentiates EADs by setting the AP plateau into the voltage range where I(Ca,L) reactivation is facilitated and I(Ks) activation is slowed.
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