ABSTRACT
Atrial fibrillation ( AF) is the most common arrhythmia in clinical practice .Mitochondrial oxidative stress is supposed to contribute to development , progression and self-perpetuation of AF .Reactive oxygen species ( ROS) is the major molecule mediating mitochondrial oxidative stress damage .ROS can alter the redox status of various molecular targets, which quite specifically leads to functional alterations of ion channel activity or activation of a variety of redox sensi -tive signal transduction pathways .Eventually , it leads to atrial electrical remodeling and promotes the development of AF . Therefore, mitochondrial oxidative stress pathways may be a new target for the therapy of atrial fibrillation .
ABSTRACT
AIM:To investigate the change of late sodium current (INaL) and the effect of Ca2+/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) inhibitor KN-93 on INaLin the cardiomyocytes after isoproterenol-induced heart fai-lure (HF) in rabbits. METHODS:The rabbit model of HF was induced by injecting isoproterenol (300 μg·kg-1· d-1) for 15 d. One month later, all rabbits received by echocardiography and HE staining to observe the morphological changes of myocardium for evaluating the HF model. The protein expression of NaV1.5, CaMKⅡδ and phosphorylated CaMKⅡδ was determined by Western blot. The ventricular myocytes were isolated from the rabbits of normal saline(NS) group and HF group by Langendorff perfusion, and the whole-cell patch-clamp technique was used to record INaL. RE-SULTS:Compared with NS group,the heart rate in HF group was increased (P<0.01), the ventricular cavity was en-larged (P<0.05),and the cardiac function was decreased(P<0.01). Compared with NS group,the cardiomyocytes in HF group arranged in disorder, vacuolar degeneration and myocardial interstitial edema were observed, and fibrous tissue increased. The protein levels of NaV1.5,CaMKⅡδ and phosphorylated CaMKⅡδ in HF group were higher than those in NS group(P<0.01). INaLin HF group significantly increased compared with NS group (P<0.01). After adding sea anemone toxin Ⅱ (ATXⅡ), the density of INaLin HF group and NS group was significantly increased, but that in HF group increased more obviously than that in NS group (P<0.01). After ATXⅡ had induced stable current, we added KN-93 into NS group and HF group,and we found that the ATXⅡ-increased INaLin NS group and HF group was signifi-cantly decreased(P<0.05).CONCLUSION:CaMKⅡinhibitor KN-93 inhibits the increase in INaLin HF rabbits,which may be related to the activity of CaMKⅡδ and the regulation of CaMKⅡ δ on INaL.
ABSTRACT
Atrial fibrillation ( AF) is the most common arrhythmia in clinical practice .Mitochondrial oxidative stress is supposed to contribute to development , progression and self-perpetuation of AF .Reactive oxygen species ( ROS) is the major molecule mediating mitochondrial oxidative stress damage .ROS can alter the redox status of various molecular targets, which quite specifically leads to functional alterations of ion channel activity or activation of a variety of redox sensi -tive signal transduction pathways .Eventually , it leads to atrial electrical remodeling and promotes the development of AF . Therefore, mitochondrial oxidative stress pathways may be a new target for the therapy of atrial fibrillation .