Mechanism of electrical remodeling of atrial myocytes and its influence on susceptibility to atrial fibrillation in diabetic rats

To explore the atrial electrical remodeling and the susceptibility of atrial fibrillation (AF) in diabetic rats. Zucker diabetic fatty (ZDF) rats were chosen as diabetic animal model, and age-matched non-diabetic littermate Zucker lean (ZL) rats as control. AF susceptibility was determined by electrophysiological examination. The current density of Ito, IKur and ICa-L were detected by whole-cell patch-clamp technique, and ion channel protein expression in atrial tissue and HL-1 cells treated with advanced glycation end products (AGE) was analyzed by western blotting. Diabetic rats had significantly enlarged left atria and evenly thickened ventricular walls, hypertrophied cells and interstitial fibrosis in atrial myocardium, increased AF susceptibility, and prolonged AF duration after atrial burst stimulation. Compared with atrial myocytes isolated from ZL controls, atrial myocytes isolated from ZDF rats had prolonged action potential duration, decreased absolute value of resting membrane potential level and current densities of Ito, IKur and ICa-L. The ion channel protein (Kv4.3, Kv1.5 and Cav1.2) expression in atrium tissue of ZDF rats and HL-1 cells treated with high concentration AGE were significantly down-regulated, compared with controls. The atrial electrical remodeling induced by hyperglycemia contributed to the increased AF susceptibility in diabetic rats.