ArticleFrontiers in physiology2012
Modeling the chronotropic effect of isoprenaline on rabbit sinoatrial node.
Article in Frontiers in physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 21 citations in OpenAlex.
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- Identification of potential candidate genes and pathways in atrioventricular nodal reentry tachycardia by whole-exome sequencing.Clinical and translational medicine · 2020Article
- Circadian rhythm of cardiac electrophysiology, arrhythmogenesis, and the underlying mechanisms.Heart rhythm · 2019Review
- Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells.Stem cell research & therapy · 2017Article
- Simulation of ventricular rate control during atrial fibrillation using ionic channel blockers.Journal of arrhythmia · 2017Article
- Article
- The importance of Ca(2+)-dependent mechanisms for the initiation of the heartbeat.Frontiers in physiology · 2015Review
- Isoprenaline: a potential contributor in sick sinus syndrome--insights from a mathematical model of the rabbit sinoatrial node.TheScientificWorldJournal · 2014Article
- Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials.Frontiers in physiology · 2014Article
- Importance of gradients in membrane properties and electrical coupling in sinoatrial node pacing.PloS one · 2014Article
- A novel computational sheep atria model for the study of atrial fibrillation.Interface focus · 2013Article
- Hyperpolarization-activated current, If, in mathematical models of rabbit sinoatrial node pacemaker cells.BioMed research international · 2013Review
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Authors and funding
7 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
introductionβ-adrenergic stimulation increases the heart rate by accelerating the electrical activity of the pacemaker of the heart, the sinoatrial node (SAN). Ionic mechanisms underlying the actions of β-adrenergic stimulation are not yet fully understood. Isoprenaline (ISO), a β-adrenoceptor agonist, shifts voltage-dependent I(f) activation to more positive potentials resulting in an increase of I(f), which has been suggested to be the main mechanism underlying the effect of β-adrenergic stimulation. However, ISO has been found to increase the firing rate of rabbit SAN cells when I(f) is blocked. ISO also increases I(CaL), I(st), I(Kr), and I(Ks); and shifts the activation of I(Kr) to more negative potentials and increases the rate of its deactivation. ISO has also been reported to increase the intracellular Ca(2+) transient, which can contribute to chronotropy by modulating the "Ca(2+) clock." The aim of this study was to analyze the ionic mechanisms underlying the positive chronotropy of β-adrenergic stimulation using two distinct and well established computational models of the electrical activity of rabbit SAN cells. METHODS AND
resultsWe modified the Boyett et al. (2001) and Kurata et al. (2008) models of electrical activity for the central and peripheral rabbit SAN cells by incorporating equations for the known dose-dependent actions of ISO on various ionic channel currents (I(CaL), I(st), I(Kr), and I(Ks)), kinetics of I(Kr) and I(f), and the intracellular Ca(2+) transient. These equations were constructed from experimental data. To investigate the ionic basis of the effects of ISO, we simulated the chronotropic effect of a range of ISO concentrations when ISO exerted all its actions or just a subset of them.
conclusionIn both the Boyett et al. and Kurata et al. SAN models, the chronotropic effect of ISO was found to result from an integrated action of ISO on I(CaL), I(f), I(st), I(Kr), and I(Ks), among which an increase in the rate of deactivation of I(Kr) plays a prominent role, though the effect of ISO on I(f) and [Ca(2+)](i) also plays a role.
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