Author + information
- Received December 4, 2009
- Revision received January 28, 2010
- Accepted February 15, 2010
- Published online May 25, 2010.
- Ricardo Caballero, BPharm, PhD⁎,
- Marta González de la Fuente, BPharm⁎,
- Ricardo Gómez, BPharm⁎,
- Adriana Barana, BSci⁎,
- Irene Amorós, BPharm⁎,
- Pablo Dolz-Gaitón, BSci⁎,
- Lourdes Osuna⁎,
- Jesús Almendral, MD, PhD†,
- Felipe Atienza, MD, PhD†,
- Francisco Fernández-Avilés, MD, PhD†,
- Ana Pita, MD†,
- Jorge Rodríguez-Roda, MD†,
- Ángel Pinto, MD, PhD†,
- Juan Tamargo, MD, PhD⁎ and
- Eva Delpón, BPharm, PhD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Eva Delpón, Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
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 Ito1gradient 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 IKurgradient 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 Ito1and IKurdifferentially in each atrium and increases IKsin both atria, an effect that further promotes re-entry.
- chronic atrial fibrillation
- voltage-dependent potassium channels
- electrical remodeling
- human myocytes
- slow delayed rectifier
Supported by Centro Nacional de Investigaciones Cardiovasculares(CNIC-13), Ministerio de Ciencia e Innovación(SAF2008-04903), Instituto de Salud Carlos III(Red HERACLES RD06/0009and PI080665), and Fundación LILLYgrants. Dr. Atienza has served as a consultant to Medtronic and received research grant support from St. Jude Medical. Drs. Caballero and González de la Fuente contributed equally to this work.
- Received December 4, 2009.
- Revision received January 28, 2010.
- Accepted February 15, 2010.
- American College of Cardiology Foundation