Yan Guo1,2,3, Cui Zhang1,2,3, Bo Shen4,5,6, Bo Yang7,8,9, Xiuhuan Chen1,2,3, Xin Liu1,2,3, Tianxin Ye1,2,3, Yuhong Fo1,2,3, Shaobo Shi1,2,3, Chuan Qu1,2,3, Jinjun Liang1,2,3. 1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China. 2. Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China. 3. Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China. 4. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China. 826534083@qq.com. 5. Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China. 826534083@qq.com. 6. Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China. 826534083@qq.com. 7. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China. yybb112@whu.edu.cn. 8. Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China. yybb112@whu.edu.cn. 9. Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China. yybb112@whu.edu.cn.
Abstract
RATIONALE: It has been reported that patients with major depressive disorder (MDD) are prone to developing ventricular arrhythmias. Moreover, the Sigma-1 receptor not only plays a crucial role in MDD but has also been shown to have antiarrhythmic properties. The Sigma-1 receptor is a common receptor related to depression and ventricular arrhythmias. OBJECTIVE: We analyzed the effects of the Sigma-1 receptor on depression and ventricular repolarization-related ion remodeling in MDD rats. METHODS: MDD was induced in rats by chronic unpredictable mild stress (CUMS), and 28 days later, the rats were subjected to behavior tests. Protein expression was measured by western blotting, and cardiac morphological changes were observed by Masson staining. Electrophysiological measurement of the myocardium was performed with the whole-cell patch-clamp technique. RESULTS: Compared with the control rats, the MDD rats exhibited lower transient outward potassium current (Ito) and L-type calcium current (ICa-L) amplitudes. On the other hand, a trend of depolarization of Ito and hyperpolarization of ICa-L was observed in the MDD rats. Thus, we investigated the effect of fluvoxamine, a Sigma-1 receptor agonist, on Ito and ICa-L. Fluvoxamine enhanced Ito and altered its current kinetics, as shown by acceleration of activation and recovery from inactivation. In contrast, fluvoxamine inhibited the Ca2+ by hyperpolarizing the steady-state activation of ICa-L. All these effects were blocked by BD1047. CONCLUSION: Taken together, our results indicate that Sigma-1 receptor modulates the functions of Ito and ICa-L to possibly exert antiarrhythmic effects.
RATIONALE: It has been reported that patients with major depressive disorder (MDD) are prone to developing ventricular arrhythmias. Moreover, the Sigma-1 receptor not only plays a crucial role in MDD but has also been shown to have antiarrhythmic properties. The Sigma-1 receptor is a common receptor related to depression and ventricular arrhythmias. OBJECTIVE: We analyzed the effects of the Sigma-1 receptor on depression and ventricular repolarization-related ion remodeling in MDDrats. METHODS:MDD was induced in rats by chronic unpredictable mild stress (CUMS), and 28 days later, the rats were subjected to behavior tests. Protein expression was measured by western blotting, and cardiac morphological changes were observed by Masson staining. Electrophysiological measurement of the myocardium was performed with the whole-cell patch-clamp technique. RESULTS: Compared with the control rats, the MDDrats exhibited lower transient outward potassium current (Ito) and L-type calcium current (ICa-L) amplitudes. On the other hand, a trend of depolarization of Ito and hyperpolarization of ICa-L was observed in the MDDrats. Thus, we investigated the effect of fluvoxamine, a Sigma-1 receptor agonist, on Ito and ICa-L. Fluvoxamine enhanced Ito and altered its current kinetics, as shown by acceleration of activation and recovery from inactivation. In contrast, fluvoxamine inhibited the Ca2+ by hyperpolarizing the steady-state activation of ICa-L. All these effects were blocked by BD1047. CONCLUSION: Taken together, our results indicate that Sigma-1 receptor modulates the functions of Ito and ICa-L to possibly exert antiarrhythmic effects.
Entities:
Keywords:
Ionic remodeling; Major depressive disorder; Sigma-1 receptor; Ventricular arrhythmia