In Humans, Chronic Atrial Fibrillation Decreases the Transient Outward Current and Ultrarapid Component of the Delayed Rectifier Current Differentially on Each Atria and Increases the Slow Component of the Delayed Rectifier Current in Both

• Published in: Journal of the American College of Cardiology 2010-05, Vol.55 (21), p.2346-2354
• Main Authors: Caballero, Ricardo, BPharm, PhD, de la Fuente, Marta González, BPharm, Gómez, Ricardo, BPharm, Barana, Adriana, BSci, Amorós, Irene, BPharm, Dolz-Gaitón, Pablo, BSci, Osuna, Lourdes, Almendral, Jesús, MD, PhD, Atienza, Felipe, MD, PhD, Fernández-Avilés, Francisco, MD, PhD, Pita, Ana, MD, Rodríguez-Roda, Jorge, MD, Pinto, Ángel, MD, PhD, Tamargo, Juan, MD, PhD, Delpón, Eva, BPharm, PhD
• Format: Article
• Language: English
• Subjects: Atrial Fibrillation - diagnosis; Atrial Fibrillation - drug therapy; Atrial Fibrillation - physiopathology; Cardiac arrhythmia; Cardiology; Cardiovascular; Cardiovascular disease; chronic atrial fibrillation; Chronic Disease; electrical remodeling; Electrocardiography; Electrophysiology; Female; Gene expression; Heart Atria - cytology; Heart Atria - metabolism; human myocytes; Humans; Internal Medicine; Ion Channel Gating - drug effects; Male; Membrane Potentials - drug effects; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - physiology; Patch-Clamp Techniques; Potassium Channel Blockers - pharmacology; Potassium Channels - drug effects; Potassium Channels - metabolism; Protein expression; Sampling Studies; slow delayed rectifier; Studies; voltage-dependent potassium channels
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2010.02.028

Objectives The purpose of this study was to compare the voltage-dependent K+ currents of human cells of the right and left atria and determine whether electrical remodeling produced by chronic atrial fibrillation (CAF) is chamber-specific. Background Several data point to the existence of interatrial differences in the repolarizing currents. Therefore, it could be possible that CAF-induced electrical remodeling differentially affects voltage-dependent K+ currents in each atrium. Methods Currents were recorded using the whole-cell patch-clamp in myocytes from left (LAA) and right atrial appendages (RAA) obtained from sinus rhythm (SR) and CAF patients. Results In SR, LAA and RAA myocytes were divided in 3 types, according to their main voltage-dependent repolarizing K+ current. CAF differentially modified the proportion of these 3 types of cells on each atrium. CAF reduced the Ca2+ -independent 4-aminopyridine-sensitive component of the transient outward current (Ito1 ) more markedly in the LAA than in the RAA. Therefore, an atrial right-to-left Ito1 gradient was created by CAF. In contrast, the ultrarapid component of the delayed rectifier current (IKur ) was more markedly reduced in the RAA than in the LAA, thus abolishing the atrial right-to-left IKur gradient observed in SR. Importantly, in both atria, CAF increased the slow component of the delayed rectifier current (IKs ). Conclusions Our results demonstrated that in SR there are intra-atrial heterogeneities in the repolarizing currents. CAF decreases Ito1 and IKur differentially in each atrium and increases IKs in both atria, an effect that further promotes re-entry.