125889 20241125101134.0 doi 10.1016/j.compbiomed.2023.106719 sideral 133420 ART-2023-133420 eng Celotto, Ch. Universidad de Zaragoza Steady-state and transient effects of SK channel block and adrenergic stimulation to counteract acetylcholine-induced arrhythmogenic effects in the human atria: a computational study 2023 Access copy available to the general public Unrestricted Hyperactivity of the parasympathetic nervous system has been linked to the development of paroxysmal atrial fibrillation (AF). The parasympathetic neurotransmitter acetylcholine (ACh) causes a reduction in action potential (AP) duration (APD) and an increase in resting membrane potential (RMP), both of which contribute to enhance the risk for reentry. Research suggests that small-conductance calcium activated potassium (SK) channels may be an effective target for treating AF. Therapies targeting the autonomic nervous system, either alone or in combination with other drugs, have been explored and have been shown to decrease the incidence of atrial arrhythmias. This study uses computational modeling and simulation to examine the impact of SK channel block (SKb) and-adrenergic stimulation through Isoproterenol (Iso) on countering the negative effects of cholinergic activity in human atrial cell and 2D tissue models. The steady-state effects of Iso and/or SKb on AP shape, APD at 90% repolarization (APD90) and RMP were evaluated. The ability to terminate stable rotational activity in cholinergically-stimulated 2D tissue models of AF was also investigated. A range of SKb and Iso application kinetics, which reflect varying drug binding rates, were taken into consideration. The results showed that SKb alone prolonged APD90 and was able to stop sustained rotors in the presence of ACh concentrations up to 0.01 M. Iso terminated rotors under all tested ACh concentrations, but resulted in highly-variable steady-state outcomes depending on baseline AP morphology. Importantly, the combination of SKb and Iso resulted in greater APD90 prolongation and showed promising anti-arrhythmic potential by stopping stable rotors and preventing re-inducibility. info:eu-repo/grantAgreement/ES/AEI/PID2019-105674RB-I00 info:eu-repo/grantAgreement/ES/DGA/LMP94_21 info:eu-repo/grantAgreement/ES/DGA/T39-23R info:eu-repo/grantAgreement/EC/H2020/638284/EU/Is your heart aging well? A systems biology approach to characterize cardiac aging from the cell to the body surface/MODELAGE This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 638284-MODELAGE info:eu-repo/grantAgreement/EC/H2020/766082/EU/MultidisciplinarY training network for ATrial fibRillation monItoring, treAtment and progression/MY-ATRIA This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 766082-MY-ATRIA info:eu-repo/grantAgreement/ES/MICINN/PID2019-104881RB-I00 info:eu-repo/grantAgreement/EUR/MICINN/TED2021-130459B-I00 info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 7.0 2023 BIOLOGY 7 / 109 = 0.064 2023 Q1 T1 MATHEMATICAL & COMPUTATIONAL BIOLOGY 2 / 66 = 0.03 2023 Q1 T1 ENGINEERING, BIOMEDICAL 16 / 123 = 0.13 2023 Q1 T1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS 19 / 170 = 0.112 2023 Q1 T1 1.481 2023 Health Informatics 2023 Q1 Computer Science Applications 2023 Q1 11.7 2023 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Sánchez, C. Universidad de Zaragoza (orcid)0000-0003-4273-5403 Mountris, K. A. Laguna, P. Universidad de Zaragoza (orcid)0000-0003-3434-9254 Pueyo, E. Universidad de Zaragoza (orcid)0000-0002-1960-407X 5007 520 Universidad de Zaragoza Dpto. Informát.Ingenie.Sistms. Área Ingen.Sistemas y Automát. 5008 800 Universidad de Zaragoza Dpto. Ingeniería Electrón.Com. Área Teoría Señal y Comunicac. 157 (2023), 106719 [14 pp.] Comput. biol. med. Computers in biology and medicine 0010-4825 3208579 http://zaguan.unizar.es/record/125889/files/texto_completo.pdf Versión publicada 2585881 http://zaguan.unizar.es/record/125889/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:125889 articulos driver 2024-11-22-11:59:52 ARTICLE