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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).
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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