期刊
LIFE SCIENCES
卷 257, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2020.118047
关键词
Sigma-1 receptor; Depression; Ventricular arrhythmia; Ionic remodeling; Structural remodeling
资金
- National Natural Science Foundation of China [81500278, 81800447]
- Natural Science Foundation of Hubei Province [2017CFB204]
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 (ICa-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 Ca2+/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 ICa-L and restoring I-to, in addition to ameliorating the CMUS-induced depressive symptoms and structural remodeling.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据