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Inhibitory effects of aloperine on voltage-gated Na+ channels in rat ventricular myocytes

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A Correction to this article was published on 20 September 2021

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Abstract

Aloperine (ALO), a quinolizidine alkaloid extracted from Sophora alopecuroides L., modulates hypertension, ventricular remodeling, and myocardial ischemia. However, few studies have evaluated the effects of ALO on other cardiovascular parameters. Accordingly, in this study, we used a rat model of aconitine-induced ventricular arrhythmia to assess the effects of ALO. Notably, ALO pretreatment delayed the onset of ventricular premature and ventricular tachycardia and reduced the incidence of fatal ventricular fibrillation. Moreover, whole-cell patch-clamp assays in rats’ ventricular myocyte showed that ALO (3, 10, and 30 μM) significantly reduced the peak sodium current density of voltage-gated Na+ channel currents (INa) in a concentration-dependent manner. The gating kinetics characteristics showed that the steady-state activation and recovery curve were shifted in positive direction along the voltage axis, respectively, and the steady-state inactivation curve was shifted in negative direction along the voltage axis, i.e., which was similar to the inhibitory effects of amiodarone. These results indicated that ALO had anti-arrhythmic effects, partly attributed to INa inhibition. ALO may act as a class I sodium channel anti-arrhythmia agent.

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Funding

This work was supported by the Research and Innovation Program for College Students of Yangzhou University (grant number X20200782).

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou, 225000, Jiangsu, China

    Meng-ting Li, Ya-ya Du, Fei Zhong, Jie-ru Wang, You-wei Gu, Yue Zhang, Xuan-tong Huang, Yi-zhou Deng & Zheng-xin Xu

  2. Jiangsu Key Laboratory of Animal Infectious Diseases and Zoonosis Prevention and Control, Yangzhou, 225001, China

    Zheng-xin Xu

  3. Key Laboratory of Integrative Medicine Prevention and Treatment in Jiangsu Province Room, Yangzhou, 225001, Jiangsu, China

    Zheng-xin Xu

  4. Jiangsu Key Laboratory of Non-coding RNA Basic and Clinical Transformation, Yangzhou, 225009, China

    Zheng-xin Xu

Authors
  1. Meng-ting Li
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  2. Ya-ya Du
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  3. Fei Zhong
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  4. Jie-ru Wang
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  9. Zheng-xin Xu
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Contributions

M.T.L. designed the study. Z.X.X. conducted the experiments. M.T.L. and Y.Y.D. analyzed data and performed the animal research. M.T.L., F.Z., Y.R.W., Y.W.G., X.T.H., and Y.Z.D. performed the cell research. M.T.L. wrote the manuscript. All authors have read and approved the manuscript. All authors confirm that all data were generated in-house, and that no paper mill was used.

Corresponding author

Correspondence to Zheng-xin Xu.

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Ethical approval

The Ethics Committee of Yangzhou University Medical College approved the experimental protocols (Yangzhou, China).

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The authors declare that they have no conflicts of interest.

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Highlights

• Aloperine pretreatment delayed the onset of VP and VT.

• Aloperine also decreased the incidence of VF.

• Aloperine blocked voltage-gated Na+ channels in a concentration-dependent manner.

• Aloperine may have uses as a class I sodium channel anti-arrhythmia agent.

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Li, Mt., Du, Yy., Zhong, F. et al. Inhibitory effects of aloperine on voltage-gated Na+ channels in rat ventricular myocytes. Naunyn-Schmiedeberg's Arch Pharmacol 394, 1579–1588 (2021). https://doi.org/10.1007/s00210-021-02076-4

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  • DOI: https://doi.org/10.1007/s00210-021-02076-4

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