ArticlePloS one2012
Markov models of use-dependence and reverse use-dependence during the mouse cardiac action potential.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed.
- A Mathematical Model of the Mouse Atrial Myocyte With Inter-Atrial Electrophysiological Heterogeneity.Frontiers in physiology · 2020Article
- Closed and open state dependent block of potassium channels cause opposing effects on excitability - a computational approach.Scientific reports · 2019Article
- Cardiac action potential repolarization revisited: early repolarization shows all-or-none behaviour.The Journal of physiology · 2017Review
- Revealing kinetics and state-dependent binding properties of IChaos (Woodbury, N.Y.) · 2017Article
- Article
- Multiscale Modeling in the Clinic: Drug Design and Development.Annals of biomedical engineering · 2016Review
- Computing rates of Markov models of voltage-gated ion channels by inverting partial differential equations governing the probability density functions of the conducting and non-conducting states.Mathematical biosciences · 2016Article
- The virtual heart as a platform for screening drug cardiotoxicity.British journal of pharmacology · 2015Review
- Computational Models for Predictive Cardiac Ion Channel Pharmacology.Drug discovery today. Disease models · 2014Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
The fast component of the cardiac transient outward current, I(Ktof), is blocked by a number of drugs. The major molecular bases of I(Ktof) are Kv4.2/Kv4.3 voltage-gated potassium channels. Drugs with similar potencies but different blocking mechanisms have differing effects on action potential duration (APD). We used in silico analysis to determine the effect of I(Ktof)-blocking drugs with different blocking mechanisms on mouse ventricular myocytes. We used our existing mouse model of the action potential, and developed 4 new Markov formulations for I(Ktof), I(Ktos), I(Kur), I(Ks). We compared effects of theoretical I(Ktof)-specific channel blockers: (1) a closed state, and (2) an open channel blocker. At concentrations lower or close to IC(50), the drug which bound to the open state always had a much greater effect on APD than the drug which bound to the closed state. At concentrations much higher than IC(50), both mechanisms had similar effects at very low pacing rates. However, an open state binding drug had a greater effect on APD at faster pacing rates, particularly around 10 Hz. In summary, our data indicate that drug effects on APD are strongly dependent not only on IC(50), but also on the drug binding state.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.