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Front. Physiol. | doi: 10.3389/fphys.2019.01346

The reversal effect of Sigma-1 receptor (S1R) agonist, SA4503, on atrial fibrillation after depression and its underlying mechanism study Short title: Liu et al -atrial fibrillation after depression and sigma-1 receptor

Xin Liu1, Chuan Qu1, Shaobo Shi1, Tianxin Ye1, Linglin Wang1, Steven Liu1, Cui Zhang1,  Bo Yang1 and  Dan Hu1*
  • 1Renmin Hospital, Faculty of Medical Sciences, Wuhan University, China

Aims: Sigma-1 (σ1) receptors have been investigated to play a protective role in both depression and cardiovascular disease. SA4503, known as a σ1 receptor agonist, regulates cardiac calcium and potassium channels in rat model of depression. However, it remains unknown whether SA4503 can alleviate myocardial inflammation nor conduction junctions in atrium after exposure to chronic mild stress.
Methods and Results: Male Sprague Dawley rats received 28-day treatment with SA4503, or vehicle, simultaneously with chronic mild stress. Behavior measurements were assessed after the daily doses. Additionally, multielectrode array assessment, electrophysiological study, immunohistochemistry analysis, histological analysis, and Western blot analysis were performed. Depression rats’ hearts showed abnormal electrical activity including the disordered excitation propagation and the prolonged total activation time (TAT). In addition, electrically induced atrial arrhythmias (AAs) were facilitated by depression in isolated hearts. The increased incidence and duration of electrically induced AAs were associated with reduced conduction junctions and enhanced spatial heterogeneity. Importantly, depressed rat hearts showed greater expression of inflammatory factors (TGF- and IL-6), and lower expression of gap junction proteins (CX40 and CX43). Furthermore, SA4503, partially mitigated the above indices in the depression group (P  0.01 for all groups).
Conclusions: These findings show effects of σ1R agonist SA4503 alleviates atrial myocardial inflammation and conduction junctions after chronic mild stress. SA4503 may be the promising pharmacological agent to treat depression related AAs by increasing conduction function, improving the expression of connexin 40 and 43, and reducing cardiac myocardial inflammation.

Keywords: sigma-1 receptor, Depression, conduction, Inflammation, Atrial Fibrillation

Received: 28 Aug 2019; Accepted: 10 Oct 2019.

Copyright: © 2019 Liu, Qu, Shi, Ye, Wang, Liu, Zhang, Yang and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Dan Hu, Renmin Hospital, Faculty of Medical Sciences, Wuhan University, Wuhan, 430060, Hubei Province, China, hudan0716@hotmail.com