title: The Na+/K+ pump is an important modulator of refractoriness and rotor dynamics in human atrial tissue.
abstract: Pharmacological treatment of atrial fibrillation (AF) exhibits limited efficacy. Further developments require a comprehensive characterization of ionic modulators of electrophysiology in human atria. Our aim is to systematically investigate the relative importance of ionic properties in modulating excitability, refractoriness, and rotor dynamics in human atria before and after AF-related electrical remodeling (AFER). Computer simulations of single cell and tissue atrial electrophysiology were conducted using two human atrial action potential (AP) models. Changes in AP, refractory period (RP), conduction velocity (CV), and rotor dynamics caused by alterations in key properties of all atrial ionic currents were characterized before and after AFER. Results show that the investigated human atrial electrophysiological properties are primarily modulated by maximal value of Na(+)/K(+) pump current (G(NaK)) as well as conductances of inward rectifier potassium current (G(K1)) and fast inward sodium current (G(Na)). G(NaK) plays a fundamental role through both electrogenic and homeostatic modulation of AP duration (APD), APD restitution, RP, and reentrant dominant frequency (DF). G(K1) controls DF through modulation of AP, APD restitution, RP, and CV. G(Na) is key in determining DF through alteration of CV and RP, particularly in AFER. Changes in ionic currents have qualitatively similar effects in control and AFER, but effects are smaller in AFER. The systematic analysis conducted in this study unravels the important role of the Na(+)/K(+) pump current in determining human atrial electrophysiology.
authors.affiliation: Communications Technology Group, I3A and IIS, University of Zaragoza, Zaragoza.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sánchez
authors.forename: Alberto
authors.initials: A
authors.lastname: Corrias
authors.forename: Alfonso
authors.initials: A
authors.lastname: Bueno-Orovio
authors.forename: Mark
authors.initials: M
authors.lastname: Davies
authors.forename: Jonathan
authors.initials: J
authors.lastname: Swinton
authors.forename: Ingemar
authors.initials: I
authors.lastname: Jacobson
authors.forename: Pablo
authors.initials: P
authors.lastname: Laguna
authors.forename: Esther
authors.initials: E
authors.lastname: Pueyo
authors.forename: Blanca
authors.initials: B
authors.lastname: Rodríguez
mesh_terms: D000200:Action Potentials / Q000502:physiology; D001281:Atrial Fibrillation / Q000503:physiopathology; D016275:Atrial Function / Q000502:physiology*; D003198:Computer Simulation; D006325:Heart Atria / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D008955:Models, Cardiovascular; D012032:Refractory Period, Electrophysiological / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
chemical_list: D000254:Sodium-Potassium-Exchanging ATPase