Melatonin inhibits arrhythmias induced by increased late sodium currents in ventricular myocytes
10.16438/j.0513-4870.2023-0601
- VernacularTitle:褪黑激素抑制心室肌细胞晚钠电流增大所诱发的心律失常
- Author:
Jie WEN
1
;
Han-feng LIU
2
;
Yan-yan YANG
2
;
Ze-fu ZHANG
1
;
An-tao LUO
1
;
Zhen-zhen CAO
1
;
Ji-hua MA
3
Author Information
1. Medical College of Wuhan University of Science and Technology, Wuhan 430070, China
2. College of Life Science and Health, Wuhan University of Science and Technology, Wuhan 430070, China
3. Medical College of Wuhan University of Science and Technology, Wuhan 430070, China; College of Life Science and Health, Wuhan University of Science and Technology, Wuhan 430070, China
- Publication Type:Research Article
- Keywords:
melatonin;
late sodium current;
action potential;
arrhythmia;
patch-clamp
- From:
Acta Pharmaceutica Sinica
2024;59(1):143-151
- CountryChina
- Language:Chinese
-
Abstract:
Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (INa.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC50) values of Mel on transient sodium current (INa.T) and specific INa.L opener 2 nmol·L-1 sea anemone toxins II (ATX II) increased INa.L were 686.615 and 7.37 μmol·L-1, respectively. Mel did not affect L-type calcium current (ICa.L), transient outward current (Ito), and AP. In addition, 16 μmol·L-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking INa.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).
