Prolonged QRS in Electrocardiogram and Decreased Ventricular Connexin 43 in Type 2 Diabetic Rat

Impairment of cardiac impulse conduction contributes to arrhythmogenesis in diabetes mellitus (DM) patients. Which active or passive property contributes to impairment of ventricular impulse conduction in type 2 DM rats was investigated. Electrocardiograms were obtained from type 2 DM model Otsuka Long-Evans Tokushima Fatty (OLETF) and healthy Long-Evans Tokushima Otsuka (LETO) rats. The active properties were evaluated by measuring ion channel currents, such as fast Na＋ channel current, L-type Ca2＋ channel current, transient outward current, and delayed rectifier K＋ current, in freshly-isolated single myocytes using the patch-clamp technique. The size of isolated myocytes was measured. Fibrosis was determined by Azan staining of formalinfixed ventricular sections. Connexin 43 protein (Cx43) expression was determined by Western blotting. The QRS duration in the OLETF rats was significantly longer than in the LETO rats (P ＜ 0.01). Current density/voltage relationships in the ion channels showed no difference between the LETO and OLETF ventricular myocytes. The length and width of the right ventricular myocytes was 7.5％ and 11.9％ greater, respectively, in the OLETF rats (each P ＜ 0.01). The width of the left ventricular myocytes was 10.3％ greater in the OLETF rats (P ＜ 0.01). The degree of perivascular and interstitial fibrosis showed no difference between the LETO and OLETF ventricles. Connexin 43 showed a significant decrease in the OLETF rat compared to in the LETO rats (P ＜ 0.05). Impulse conduction in type 2 diabetic rat ventricle may not be caused by dysfunction of ion channels, but decreased expression of Cx43.