Abstract
Background
In the present study, the electropharmacological activity of traditional Chinese medicine, Ginkgo biloba extract (GBE), on human hyperpolarization-activated nucleotide-gated (HCN) channels and the underlying “funny” currents was investigated.
Methods
Standard two-electrode voltage-clamp recordings were employed to examine the properties of cloned HCN subunit currents expressed in Xenopus oocytes under controlled conditions and GBE administration.
Results
We found that GBE irreversibly inhibited the HCN2 and HCN4 channel currents in a concentration-dependent fashion and that the HCN4 current was more sensitive to GBE compared with HCN2. In addition, GBE inhibition of the current amplitudes of HCN2 and HCN4 currents was accompanied by a decrease in the activation and deactivation kinetics.
Conclusion
The results of this study contribute toward illustrating the antiarrhythmic mechanism of GBE, which might be useful for the treatment of arrhythmia.
Zusammenfassung
Hintergrund
In der vorliegenden Studie wurde die elektropharmakologische Aktivität einer Form traditioneller chinesischer Medizin, des Ginkgo-biloba-Extrakts (GBE), auf humane hyperpolarisationsaktivierte nukleotidgesteuerte (HCN-)Kanäle und die zugrunde liegenden Ströme, „funny currents“, untersucht.
Methoden
Standardisierte Aufnahmen mit 2‑Elektroden-Spannungsklemmen wurden verwendet, um die Eigenschaften der Ströme geklonter HCN-Untereinheiten zu untersuchen, die in Xenopus-Oozyten unter kontrollierten Bedingungen und Anwendung von GBE exprimiert wurden.
Ergebnisse
Die Autoren stellten fest, dass GBE die HCN2- und HCN4-Kanalströme konzentrationsabhängig irreversibel hemmte und dass der HCN4-Strom empfindlicher auf GBE reagierte als HCN2. Darüber hinaus trat als Begleiterscheinung der GBE-Inhibition bei den Stromamplituden der HCN2- und HCN4-Ströme eine Verminderung der Aktivierungs- und Deaktivierungskinetik auf.
Schlussfolgerung
Die Ergebnisse der vorliegenden Studie tragen zur Veranschaulichung der antiarrhythmischen Mechanismen des GBE bei, welcher sich möglicherweise für die Behandlung von Arrhythmien eignet.
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Funding
This work was supported by the National Science Foundation for Distinguished Young Scholars of China under Grant No. 81500255, and Hubei Provincial Natural Science Foundation of China under Grant No. 2018CFB420.
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H. Chen, Y. Chen, J. Yang, P. Wu, X. Wang and C. Huang declare that they have no competing interests.
For this article no studies with human participants were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case. The animals used in the study were treated in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and all the experimental methods were approved by the Animal Research Committee of the First Clinic College of Wuhan University (Wuhan, China).
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Chen, H., Chen, Y., Yang, J. et al. Effect of Ginkgo biloba extract on pacemaker channels encoded by HCN gene. Herz 46, 255–261 (2021). https://doi.org/10.1007/s00059-020-04933-z
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DOI: https://doi.org/10.1007/s00059-020-04933-z