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Magnesium isoglycyrrhizinate inhibits L-type Ca2+ channels, Ca2+ transients, and contractility but not hERG K+ channels

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Abstract

To explore the cardiovascular protective effects of Magnesium isoglycyrrhizinate (MI), especially the underlying cellular mechanisms related to L-type calcium channels and myocardial contractility, and to examine the effects of MI on hERG K+ current expressed in HEK293 cells. We used the whole-cell patch clamp technique, video-based edge detection and dual excitation fluorescence photomultiplier systems to explore the effect of MI on L-type Ca2+ currents (ICa-L) and cell contraction in rat cardiomyocytes. We also examined the rapidly activating delayed rectifier potassium current (IKr) expressed in HEK293 cells using a perforated patch clamp. MI inhibited ICa-L in a dose-dependent manner, with a half-maximal inhibitory concentration (IC50) of 0.22 mg/ml, and the maximal inhibitory effect was 61.10 ± 0.59%. MI at a concentration of 0.3 mg/ml reduced cell shortening by 24.12 ± 3.97% and the peak value of the Ca2+ transient by 36.54 ± 4.96%. MI had no significant influence on hERG K+ channels expressed in HEK293 cells at all test potentials. MI exerts protective effects on the heart via the inhibition of ICa-L and cell shortening in rat cardiomyocytes. However, MI had no significant influence on IKr; thus, MI may exert cardioprotective effects without causing drug-induced long QT syndrome.

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Acknowledgements

This work was supported by the Research Foundation of Administration of Traditional Chinese Medicine of Hebei Province, China (Nos. 2017007 and 2015030), Research Foundation of Education Bureau of Hebei Province (QN20131046 to X.Z.), and Key Basic Applied Project of Hebei Provincial Department of Science & Technology (No. 15967730D to W.Z.).

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    Authors and Affiliations

    1. Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang, 050200, Hebei, China

      Yue Lin, Yuanyuan Zhang, Xue Han, Ying Zhang, Xuan Zhang, Fenghua Zhang, Li Chu & Jianping Zhang

    2. Hebei Medical University, No.361, Zhongshan East Road, Shijiazhuang, 050017, Hebei, China

      Qiongtao Song & Tao Song

    3. Department of Pharmacy, The Fourth Hospital of Hebei Medical University, No.12, Jiankang Road, Shijiazhuang, 050011, Hebei, China

      Xi Chu

    4. Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang, 050200, Hebei, China

      Yue Lin, Yuanyuan Zhang, Xuan Zhang, Li Chu & Jianping Zhang

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    Yue Lin and Yuanyuan Zhang contributed equally to this work.

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    Lin, Y., Zhang, Y., Song, Q. et al. Magnesium isoglycyrrhizinate inhibits L-type Ca2+ channels, Ca2+ transients, and contractility but not hERG K+ channels. Arch. Pharm. Res. 40, 1135–1145 (2017). https://doi.org/10.1007/s12272-017-0938-6

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