000106724 001__ 106724
000106724 005__ 20231006143258.0
000106724 0247_ $$2doi$$a10.1109/EMBC44109.2020.9175886
000106724 0248_ $$2sideral$$a120314
000106724 037__ $$aART-2020-120314
000106724 041__ $$aeng
000106724 100__ $$aCelotto, Chiara$$uUniversidad de Zaragoza
000106724 245__ $$aSK Channel Block and Adrenergic Stimulation Counteract Acetylcholine-Induced Arrhythmogenic Effects in Human Atria
000106724 260__ $$c2020
000106724 5060_ $$aAccess copy available to the general public$$fUnrestricted
000106724 5203_ $$aThere is increasing evidence on the role of the autonomic nervous system in the pathogenesis of atrial fibrillation. Interventions targeting autonomic modulation of atrial electrical activity have been shown to reduce the incidence of atrial arrhythmias. Additionally, recent investigations have proved that pharmacological therapies inhibiting small-conductance calcium-activated potassium (SK) channels are able to lessen cholinergic effects in the atria.In this study we use computational modeling and simulation to test individual and combined effects of SK channel block and adrenergic stimulation in counteracting detrimental effects induced by the parasympathetic neurotransmitter acetylcholine (ACh) on human atrial electrophysiology. Cell and tissue models are built that incorporate descriptions of SK channels as well as of isoproterenol (Iso)- and ACh-mediated regulation of the atrial action potential (AP). Three different cellular AP models, representing a range of physiological AP shapes, are considered and both homogeneous and heterogeneous ACh distributions in atrial tissue are simulated.At the cellular level, SK channel block is demonstrated to partially revert shortening of AP duration (APD) mediated by ACh at various doses, whereas 1 µM Iso has a variable response depending on the AP shape. The combination of SK block and Iso is in all cases able to take APD back to baseline levels, recovering between 82% and 120% of the APD shortening induced by 0.1 µM ACh. At the tissue level, SK block and Iso alone or in combination do not exert remarkable effects on conduction velocity, but the combination of the two is able to notably prolong the ACh-mediated APD shortening, thus increasing the wavelength for reentry.In conclusion, the results from this study support the combination of SK channel block and adrenergic stimulation as a potential option to counteract parasympathetically-mediated proarrhythmic effects in the human atria.
000106724 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/T39-17R-BSICoS$$9info:eu-repo/grantAgreement/ES/DGA/LMP124-18$$9info:eu-repo/grantAgreement/EUR/ERC-2014-StG-638284$$9info:eu-repo/grantAgreement/EC/H2020/766082/EU/MultidisciplinarY training network for ATrial fibRillation monItoring, treAtment and progression/MY-ATRIA$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 766082-MY-ATRIA$$9info:eu-repo/grantAgreement/ES/MINECO/DPI2016-75458-R
000106724 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000106724 655_4 $$ainfo:eu-repo/semantics/conferenceObject$$vinfo:eu-repo/semantics/acceptedVersion
000106724 700__ $$0(orcid)0000-0003-4273-5403$$aSánchez, Carlos
000106724 700__ $$0(orcid)0000-0003-2946-3044$$aMountris, Konstantinos A.
000106724 700__ $$0(orcid)0000-0003-3434-9254$$aLaguna, Pablo$$uUniversidad de Zaragoza
000106724 700__ $$0(orcid)0000-0002-1960-407X$$aPueyo, Esther$$uUniversidad de Zaragoza
000106724 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000106724 773__ $$g2020-July (2020), 2303-2306$$pConf. proc. (IEEE Eng. Med. Biol. Soc., Conf.)$$tConference proceedings (IEEE Engineering in Medicine and Biology Society. Conf.)$$x1557-170X
000106724 8564_ $$s947601$$uhttps://zaguan.unizar.es/record/106724/files/texto_completo.pdf$$yPostprint
000106724 8564_ $$s3495416$$uhttps://zaguan.unizar.es/record/106724/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000106724 909CO $$ooai:zaguan.unizar.es:106724$$particulos$$pdriver
000106724 951__ $$a2023-10-06-14:06:22
000106724 980__ $$aARTICLE