Korean J Intern Med.  2010 Dec;25(4):377-385. 10.3904/kjim.2010.25.4.377.

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

• Oh S
• Kim KB
• Ahn H
• Cho HJ
• Choi YS

• KMID: 964718
• DOI: http://doi.org/10.3904/kjim.2010.25.4.377

Abstract

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 Ca2+ channels, ryanodine receptor (RyR2), sarcoplasmic reticular Ca2+-ATPase (SERCA2), gene encoding the rapid component of the delayed rectifier Ikr (HERG), gene encoding calcium-independent transient outward current I(to1) (Kv4.3), gene encoding the ultrarapid component of the delayed rectifier Iku (Kv1.5), K+ channel-interacting protein 2 (KChIP2), hyperpolarization-activated cation channel 2 associated with the pacemaker current If (HCN2), and gene encoding Na+ channel (SCN5A).
RESULTS
Reduced L-type Ca2+ 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.

Keyword

Atrial fibrillation; Electrical remodeling; Ion channels

MeSH Terms

Adult
Aged
Aortic Valve Stenosis/metabolism
Atrial Fibrillation/*metabolism
Calcium/metabolism
Chronic Disease
Coronary Artery Disease/metabolism
Female
Heart Valve Diseases/*metabolism
Humans
Ion Channels/*genetics
Male
Middle Aged
*Mitral Valve
Potassium Channels/genetics
Ryanodine Receptor Calcium Release Channel/genetics
Sodium Channels/genetics