Moricizine prevents atrial fibrillation by late sodium current inhibition in atrial myocytes

Abstract

Background: Enhanced late sodium current (INaL) is reportedly related to an increased risk of atrial fibrillation (AF). Moricizine, as a widely used anti-arrhythmia drug for suppressing ventricular tachycardia, has also been shown to prevent paroxysmal AF. However, the mechanism of its therapeutic effect remains poorly understood.Methods: Angiotensin II (Ang II) was induced in C57Bl/6 mice (male wild-type) for 4 weeks to increase the susceptibility of AF, and acetylcholine-calcium chloride was used to induce AF. The whole-cell patch-clamp technique was used to detect INaL from isolated atrial myocytes. The expression of proteins in atrial of mice and HL-1 cells were examined by Western-blot. Results:The results showed that moricizine significantly inhibited Ang II-mediated atrial enlargement and reduced AF vulnerability. We found that the densities of INaL were enhanced in Ang II-treated left and right atrial cardiomyocytes. Simultaneously, the Ang II-induced increase in INaL currents density was alleviated by the administration of moricizine, and no alteration in Nav1.5 expression was observed. In normal isolated atrial myocytes, moricizine significantly reduced Sea anemone toxin II (ATX II)-enhanced INaL density with a reduction of peak sodium currents. In addition, moricizine reduced the Ang II-induced upregulation of phosphorylated calcium/calmodulin-dependent protein kinase-II (p-CaMKII) in both the left and right atria.In HL-1 cells, moricizine also reduced the upregulation of p-CaMKII with Ang II and ATX II intervention, respectively. Conclusions: Our results indicate that Ang II enhances the INaL via activation of CaMKII. Moricizine inhibits INaL and reduces CaMKII activation, which may be one of the mechanisms of moricizine suppression of AF.

Atrial-esophageal fistula after atrial fibrillation ablation: a case report and literature review

“…In recent years, the incidence of atrial fibrillation (AF) has been growing with the aging of the population. The treatment of AF mainly includes antiarrhythmic drugs and surgery ( 1 ). Catheter ablation, as a new technology of surgery, has become one of the main methods to treat AF due to its advantages of less trauma, low recurrence rate, and high success rate ( 2 ).…”

The inter-chamber differences in the contractile function between left and right atrial cardiomyocytes in atrial fibrillation in rats

“…Additionally, high extracellular Ca 2+ levels may increase the release of norepinephrine from sympathetic end terminals ( 48 , 49 ). This together results in a decrease in the atrial effective refractory period creating an atrial substrate for AF and in an increase of the incidence of inducible AF and its duration, reflecting the pathological process of AF ( 8 , 21 ).…”

“…The different roles of the left (LA) and right (RA) atria in the initiation and maintenance of AF have been widely debated. Previous studies showed that LA is typically the location of high-frequency sources in both paroxysmal and chronic AF resulting in LA-to-RA frequency differences during AF, which are associated with inter-atrial differences in structure and K + and Na + channel proteins (4)(5)(6)(7)(8). LA fibrosis may have a greater impact on AF initiation and maintenance than RA fibrosis, which also may contribute to LAto-RA frequency differences during AF (6,9,10).…”

Effects of Moracizine Combined with Metoprolol on Hemodynamic Indices of the Left Atrium and Quality of Life in Patients with Atrial Fibrillation

“…The latter drugs can accelerate the second and third phases of repolarization, thereby shortening the action potential duration and prolonging the effective refractory period. A study of moracizine treatment for atrial arrhythmias found that it significantly reduced the incidence of AF and of AF burden without affecting the sinus rhythm [5]. Metoprolol is a selective β1 receptor blocker that can reduce the heart rate and cardiac output (CO) at rest and during exercise, reduce blood pressure, and slow atrioventricular conduction to decrease the sinus rhythm [6].…”