title: A Mathematical Model of Neonatal Rat Atrial Monolayers with Constitutively Active Acetylcholine-Mediated K+ Current.
abstract: Atrial fibrillation (AF) is the most frequent form of arrhythmia occurring in the industrialized world. Because of its complex nature, each identified form of AF requires specialized treatment. Thus, an in-depth understanding of the bases of these arrhythmias is essential for therapeutic development. A variety of experimental studies aimed at understanding the mechanisms of AF are performed using primary cultures of neonatal rat atrial cardiomyocytes (NRAMs). Previously, we have shown that the distinct advantage of NRAM cultures is that they allow standardized, systematic, robust re-entry induction in the presence of a constitutively-active acetylcholine-mediated K+ current (IKACh-c). Experimental studies dedicated to mechanistic explorations of AF, using these cultures, often use computer models for detailed electrophysiological investigations. However, currently, no mathematical model for NRAMs is available. Therefore, in the present study we propose the first model for the action potential (AP) of a NRAM with constitutively-active acetylcholine-mediated K+ current (IKACh-c). The descriptions of the ionic currents were based on patch-clamp data obtained from neonatal rats. Our monolayer model closely mimics the action potential duration (APD) restitution and conduction velocity (CV) restitution curves presented in our previous in vitro studies. In addition, the model reproduces the experimentally observed dynamics of spiral wave rotation, in the absence and in the presence of drug interventions, and in the presence of localized myofibroblast heterogeneities.
authors.affiliation: Laboratory of Experimental Cardiology, Department of Cardiology, Heart Lung Center Leiden, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Rupamanjari
authors.initials: R
authors.lastname: Majumder
authors.affiliation: Laboratory of Experimental Cardiology, Department of Cardiology, Heart Lung Center Leiden, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Wanchana
authors.initials: W
authors.lastname: Jangsangthong
authors.affiliation: Laboratory of Experimental Cardiology, Department of Cardiology, Heart Lung Center Leiden, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Iolanda
authors.initials: I
authors.lastname: Feola
authors.affiliation: Laboratory of Experimental Cardiology, Department of Cardiology, Heart Lung Center Leiden, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Dirk L
authors.initials: DL
authors.lastname: Ypey
authors.affiliation: Laboratory of Experimental Cardiology, Department of Cardiology, Heart Lung Center Leiden, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Daniël A
authors.initials: DA
authors.lastname: Pijnappels
authors.affiliation: Department of Physics and Astronomy, Ghent University, Ghent, Belgium.|Moscow Institute of Physics and Technology, (State University), Dolgoprudny, Moscow Region, Russia.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Panfilov
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D016275:Atrial Function / Q000502:physiology*; D003198:Computer Simulation; D015640:Ion Channel Gating / Q000502:physiology; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000502:physiology
chemical_list: D015222:Sodium Channels; D000109:Acetylcholine; D011188:Potassium