Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China.
Psychopharmacology (Berl). 2021 Feb;238(2):487-499. doi: 10.1007/s00213-020-05697-4. Epub 2020 Nov 2.
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.
We analyzed the effects of the Sigma-1 receptor on depression and ventricular repolarization-related ion remodeling in MDD rats.
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.
Compared with the control rats, the MDD rats exhibited lower transient outward potassium current (Ito) and L-type calcium current (I) amplitudes. On the other hand, a trend of depolarization of I and hyperpolarization of I was observed in the MDD rats. Thus, we investigated the effect of fluvoxamine, a Sigma-1 receptor agonist, on Ito and I. Fluvoxamine enhanced Ito and altered its current kinetics, as shown by acceleration of activation and recovery from inactivation. In contrast, fluvoxamine inhibited the Ca by hyperpolarizing the steady-state activation of I. All these effects were blocked by BD1047.
Taken together, our results indicate that Sigma-1 receptor modulates the functions of Ito and I to possibly exert antiarrhythmic effects.
据报道，患有重度抑郁症（MDD）的患者易发生室性心律失常。此外，Sigma-1 受体不仅在 MDD 中起关键作用，而且还具有抗心律失常特性。Sigma-1 受体是一种与抑郁和室性心律失常相关的常见受体。
我们分析了 Sigma-1 受体对 MDD 大鼠抑郁和与心室复极相关的离子重构的影响。
通过慢性不可预测轻度应激（CUMS）诱导大鼠 MDD，28 天后，对大鼠进行行为测试。通过 Western blot 测量蛋白质表达，通过 Masson 染色观察心脏形态变化。用电生理全细胞膜片钳技术测量心肌电生理。
与对照组大鼠相比，MDD 大鼠的瞬时外向钾电流（Ito）和 L 型钙电流（I）幅度较低。另一方面，在 MDD 大鼠中观察到 Ito 和 I 的去极化趋势和 hyperpolarization。因此，我们研究了 Sigma-1 受体激动剂 fluvoxamine 对 Ito 和 I 的影响。Fluvoxamine 增强了 Ito 并改变了其电流动力学，表现为激活和失活恢复的加速。相比之下，Fluvoxamine 通过 hyperpolarization I 的稳态激活来抑制 Ca。所有这些作用均被 BD1047 阻断。
综上所述，我们的结果表明 Sigma-1 受体调节 Ito 和 I 的功能，可能发挥抗心律失常作用。
