Yaoxu Chen,Chunxia Yin,Yingying Yang,Zhuo Fan,Jinling Shang,Wen Tan
Ischemia/reperfusion (I/R) induces prolongation of QT interval and action potential duration (APD), which is a major cardiac electrical disorder in patients with arrhythmias. However, the mechanism of QT interval prolongation induced by I/R remains unclear. In the present study, we hypothesized that the rapid component of delayed rectifier potassium ( I Kr ) channel plays an important role in I/R-induced QT interval prolongation. We observed a marked attenuation of I Kr and a significant prolongation of action potential duration (APD) in a simulated I/R system with sodium dithionite (Na 2 S 2 O 4 ) in ventricular myocytes of guinea pigs. The I Kr current density was inhibited by 64% and APD increased by 87% respectively. Moreover, the inhibition of I Kr is primarily ascribed to overproduction of reactive oxygen species (ROS) by I/R, which can be partly reversed by antioxidant vitamin E (100 μmol/L). The value of I Kr tail current density increased from 0.516 ± 0.040 pA/pF in I/R to 0.939 ± 0.091 pA/pF when treated with vitamin E. Moreover, we also demonstrated that QTc interval was increased by I/R and reversed by Vitamin E in isolated guinea pig hearts. In conclusion, the inhibition of I Kr is one of the underlying mechanisms of prolongation of QT interval and APD in I/R. Vitamin E might have a benefit in coronary reperfusion therapy .
Aim The purpose of the study was to investigate what effects the sigma-1 receptor (S1R) could exert on the cardiac myocyte ion channels in a rodent model of depression and to explore the underlying mechanisms since depression is an independent risk factor for cardiovascular diseases including ventricular arrhythmias (VAs). Materials and methods To establish the depression model in rats, chronic mild unpredictable stress (CMUS) for 28 days was used. The S1R agonist fluvoxamine was injected intraperitoneally from the second week to the last week for 21 days in total, and the effects were evaluated by patch clamp, western blot analysis, and Masson staining. Key findings We demonstrated that depression was improved after treatment with fluvoxamine. In addition, the prolongation of the corrected QT (QTc) interval under CMUS that increased vulnerability to VAs was significantly attenuated by stimulation of S1R due to the decreased amplitude of L-type calcium current (I Ca-L ) and the restoration of reduced transient outward potassium current (I to ) resulting from CMUS induction. The S1R also decelerated I to inactivation and accelerated I to recovery by activating Ca 2+ /calmodulin-dependent kinase II. Moreover, the stimulation of S1R ameliorated the structural remodeling as the substrate for maintenance of VAs. All these effects were abolished by the administration of S1R antagonist BD1047, which verified the roles for S1R. Significance Activation of S1R could decrease the vulnerability to VAs by inhibiting I Ca-L and restoring I to , in addition to ameliorating the CMUS-induced depressive symptoms and structural remodeling.
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