Remodeling of Ion Channel Expression in Patients with Chronic Atrial Fibrillation and Mitral Valvular Heart Disease

BACKGROUND/AIMS Underlying cardiac pathology and atrial fibrillation (AF) affect the molecular remodeling of ion channels in the atria. Changes in the expression of these molecules have not been demonstrated in Korean patients with mitral valvular heart disease. Thus, the purpose of this study was to analyze ion channel expression in patients with chronic AF and mitral valvular heart disease. METHODS A total of 17 patients (eight males and nine females; mean age, 57 ± 14 years [range, 19 to 77]) undergoing open-heart surgery were included in the study. Twelve patients (seven with coronary artery disease and five with aortic valvular disease) had sinus rhythm, and five patients (all with mitral valvular disease) had chronic, permanent AF. A piece of right atrial appendage tissue (0.5 g) was obtained during surgery. RT-PCR was used to evaluate the expression of L-type Ca(2+) channels, ryanodine receptor (RyR2), sarcoplasmic reticular Ca(2+)-ATPase (SERCA2), gene encoding the rapid component of the delayed rectifier I(kr) (HERG), gene encoding calcium-independent transient outward current I(to1) (Kv4.3), gene encoding the ultrarapid component of the delayed rectifier I(ku) (Kv1.5), K(+) channel-interacting protein 2 (KChIP2), hyperpolarization-activated cation channel 2 associated with the pacemaker current I(f) (HCN2), and gene encoding Na(+) channel (SCN5A). RESULTS Reduced L-type Ca(2+) channel, RyR2, SERCA2, Kv1.5, and KChIP2 expression and borderline increased HCN2 expression were observed in the patients with AF and mitral valvular heart disease. Left atrial diameter was negatively correlated with RyR2 and KChIP2 expression. Fractional area shortening of the left atrium was positively correlated with RyR2 and KChIP2 expression. CONCLUSIONS Alterations in ion channel expression and the anatomical substrate may favor the initiation and maintenance of AF in patients with mitral valvular heart disease.