Sigma-1 receptor ligands improves ventricular repolarization-related ion remodeling in rats with major depression disorder.

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 (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.

CONCLUSION

Taken together, our results indicate that Sigma-1 receptor modulates the functions of Ito and I to possibly exert antiarrhythmic effects.