Dual effects of the small-conductance Ca <sup>2+</sup> -activated K <sup>+</sup> current on human atrial electrophysiology and Ca <sup>2+</sup> -driven arrhythmogenesis: an in silico study
Nathaniel T. Herrera, Xianwei Zhang, Haibo Ni, Mary M. Maleckar, Jordi Heijman, Dobromir Dobrev, Eleonora Grandi, Stefano Morotti
Abstract
Using our established framework for human atrial myocyte simulations, we investigated the role of the small-conductance Ca 2+ -activated K + current ( I SK ) in the regulation of cell function and the development of Ca 2+ -driven arrhythmias. We found that I SK inhibition, a promising atrial-selective pharmacological strategy against atrial fibrillation, counteracts the reentry-promoting abbreviation of atrial refractoriness, but renders human atrial myocytes more vulnerable to delayed afterdepolarizations, thus potentially increasing the propensity for ectopic (triggered) activity.
Topics & Concepts
AfterdepolarizationRepolarizationCardiac electrophysiologyRefractory periodAtrial action potentialAtrial fibrillationElectrophysiologyEffective refractory periodInternal medicineCardiologyDepolarizationReentrySinus rhythmConductanceChemistryMedicineBiophysicsBiologyPhysicsCondensed matter physicsCardiac electrophysiology and arrhythmiasAtrial Fibrillation Management and OutcomesCardiac Arrhythmias and Treatments