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Melatonin inhibits arrhythmias induced by increased late sodium currents in ventricular myocytes
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Jie WEN1, Han-feng LIU2, Yan-yan YANG2, Ze-fu ZHANG1, An-tao LUO1, Zhen-zhen CAO1, Ji-hua MA1, 2, *
Acta Pharmaceutica Sinica | 2024, 59(1) : 143 - 151
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Acta Pharmaceutica Sinica | 2024, 59(1): 143-151
Original Articles
Melatonin inhibits arrhythmias induced by increased late sodium currents in ventricular myocytes
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Jie WEN1, Han-feng LIU2, Yan-yan YANG2, Ze-fu ZHANG1, An-tao LUO1, Zhen-zhen CAO1, Ji-hua MA1, 2, *
Affiliations
  • 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
Published: 2024-01-12 doi: 10.16438/j.0513-4870.2023-0601
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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).

melatonin  /  late sodium current  /  action potential  /  arrhythmia  /  patch-clamp
Jie WEN, Han-feng LIU, Yan-yan YANG, Ze-fu ZHANG, An-tao LUO, Zhen-zhen CAO, Ji-hua MA. Melatonin inhibits arrhythmias induced by increased late sodium currents in ventricular myocytes[J]. Acta Pharmaceutica Sinica, 2024 , 59 (1) : 143 -151 . DOI: 10.16438/j.0513-4870.2023-0601
Year 2024 volume 59 Issue 1
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Article Info
doi: 10.16438/j.0513-4870.2023-0601
  • Receive Date:2023-05-10
  • Online Date:2025-11-28
  • Published:2024-01-12
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  • Received:2023-05-10
  • Revised:2023-06-19
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Affiliations
    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
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

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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