000098278 001__ 98278
000098278 005__ 20231006143302.0
000098278 0247_ $$2doi$$a10.23919/CinC49843.2019.9005706
000098278 0248_ $$2sideral$$a121996
000098278 037__ $$aART-2019-121996
000098278 041__ $$aeng
000098278 100__ $$aCelotto, C.$$uUniversidad de Zaragoza
000098278 245__ $$aCalcium-Activated Potassium Channels Inhibition in Autonomically Stimulated Human Atrial Myocytes
000098278 260__ $$c2019
000098278 5060_ $$aAccess copy available to the general public$$fUnrestricted
000098278 5203_ $$aThe autonomic nervous system has been reported to play a major role in the generation and maintenance of atrial fibrillation. Various investigations have suggested small-conductance calcium-activated potassium (SK) channels as potential targets for more effective pharmacological therapies. In this study, we used in silico modeling and simulation to investigate the effects of SK channel inhibition on the action potential (AP) of autonomically stimulated human atrial cardiomyocytes. The Grandi AP model, with a new formulation for the ISK current, was used to represent human atrial electrophysiology. Choliner-gic stimulation by different concentrations of acetylcholine (ACh) hyperpolarized the AP and shortened the AP duration (APD) in a dose-dependent manner, with up to 7 mV resting membrane potential elevation and >200 ms APD shortening for 1 µM ACh at 1 Hz pacing frequency. Additional ß-adrenergic stimulation by 1 µM Isoproterenol (Iso) partially attenuated the effects of cholinergic stimulation by prolonging the APD by 41.6%. ISK inhibition was able to reverse the effects of cholinergic activation, but only for moderate ACh doses and when combined with 1 µM Iso, leading to 58.3% prolongation of the AP stimulated with 0.01 µM ACh. In conclusion, ISK inhibition combined with ß-adrenergic stimulation can be effective in antagonizing cholinergic effects on human atrial myocytes.
000098278 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000098278 592__ $$a0.296$$b2019
000098278 593__ $$aComputer Science (miscellaneous)$$c2019
000098278 593__ $$aCardiology and Cardiovascular Medicine$$c2019
000098278 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000098278 700__ $$0(orcid)0000-0003-4273-5403$$aSánchez, C.
000098278 700__ $$0(orcid)0000-0003-3434-9254$$aLaguna, P.$$uUniversidad de Zaragoza
000098278 700__ $$0(orcid)0000-0002-1960-407X$$aPueyo, E.$$uUniversidad de Zaragoza
000098278 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000098278 773__ $$g46 (2019), [4 pp]$$pComput. cardiol.$$tComputing in Cardiology$$x2325-8861
000098278 8564_ $$s218250$$uhttps://zaguan.unizar.es/record/98278/files/texto_completo.pdf$$yVersión publicada
000098278 8564_ $$s2711698$$uhttps://zaguan.unizar.es/record/98278/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000098278 909CO $$ooai:zaguan.unizar.es:98278$$particulos$$pdriver
000098278 951__ $$a2023-10-06-14:07:07
000098278 980__ $$aARTICLE