Effects Of Transient Outward Potassium Current On Ventricular Electrophysiological Remodeling In Diabetic Cardiomyopathy

Objective: Diabetic cardiomyopathy (DCM) is often accompany witharrhythmias, which make heart failure worse and even sudden death easily.Currently, DCM with malignant arrhythmias is considered to be involving withventricular electrophysiological remodeling. Tomaselli found that there hadobvious ventricular electrophysiological remodeling in heart failure andhypertrophic ventricles, which presented prolonged action potentialduration(APD) and effective refractory period（ERP）and delayed repolarization.However, the changes of ion currents were still not clear, but it was considered tobe association with reduction of transient outward potassium current (Ito). Therewere seldom studies for ventricular electrophysiological remodeling in diabeticcardiomyopathy, and what role the ‘Ito’ was playing is also not clear. In order tounderstand the actions of Ito in ventricular electrophysiological remodeling forDCM, this study was applied by streptozotocin(STZ) to create the rat diabeticcardiomyopathy model and measured the alterations of myocardium Ito by patchclamp technique. Methods:20healthy adult Spprague-dawley rats wereselected and divided into two groups randomly:1)Control group（n=10）and2)DCM group（n=10）. Rats in control group and DCM group were fed withnormal rat diet and high fat diet persistently12weeks, respectively. STZ wasapplied in DCM group to make the rat diabetic cardiomyopathy model byintraperitoneal injection, and, accordingly, the same dosages of citric acid buffer were used to the Control group by the same way. The myocardial pathologicalalterations of DCM were identified in DCM group by histopathologic test, andcardiomyocytes in both groups were separated by advanced calcium-tolerantseparation method. Whole-cell path clamp technique was used to record theunicellular changes of Ito and membrane capacitance in left ventricular myocytesfor DCM and control group. Clampex10.1software was used for data acquisitionand Clampfit10.1as well as OriginPro8.0software was used for data analysis.Results: Compared with control group, the serum total cholesterol (TC),triglyeride (TG),low-density lipoprotein cholesterol (LDL-C) and bloodglucose(BG) of rats in DCM group were higher (P<0.05），but the serumHigh-density lipoprotein cholesterol (HDL-C) was lower(P<0.05）. The Itocurrent density of left ventricular myocytes was significantly lower in DCMgroup（16.8±9.1pA/pF at+70mv）than in control group（36.25±5.2pA/pF at+70mv）(P<0.05）, and the I-V curve of Ito in DCM group was more depressedthan in the Control group markedly. Conclusions:1. Ito plays an important role inelectrophysiological remodeling of diabetic cardiomyopathy. The reduction of Itomay be caused by the decrease of transient outward potassium current channels,which association with cardiac electrophysiological remodeling.2. The delay ofrepolarization in phase1and prolonged of plateau in phase2and extended APDand ERP, which caused by the reduction of Ito in DCM, would generateafterdepolarization which induced arrhythmias.3. The different distribution of Itochannel in endocardial and epicardial myocardium, with the different changes ofAPD and ERP respectively, elevated the dispersion of ADP, which performed reentry pathway and would present severe arrthymias clininally, such asventricular tachycardia (VT) and ventricular fibrillation (VF).