Next Article in Journal
Galectins in Endothelial Cell Biology and Angiogenesis: The Basics
Next Article in Special Issue
Physiological and Pathophysiological Roles of Mitochondrial Na+-Ca2+ Exchanger, NCLX, in Hearts
Previous Article in Journal
Cyclodextrins as Anti-inflammatory Agents: Basis, Drugs and Perspectives
 
 
Article

The Effect of a Synthetic Estrogen, Ethinylestradiol, on the hERG Block by E-4031

1
Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
2
Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan
3
Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan
4
Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba City, Ibaraki 305-8575, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Yosuke Okamoto and Kyoichi Ono
Biomolecules 2021, 11(9), 1385; https://doi.org/10.3390/biom11091385
Received: 30 July 2021 / Revised: 15 September 2021 / Accepted: 18 September 2021 / Published: 20 September 2021
(This article belongs to the Special Issue Molecular Pathogenesis of Cardiac Arrhythmia)
Inhibition of K+-conductance through the human ether-a-go-go related gene (hERG) channel leads to QT prolongation and is associated with cardiac arrhythmias. We previously reported that physiological concentrations of some estrogens partially suppress the hERG channel currents by interacting with the S6 residue F656 and increase the sensitivity of hERG blockade by E-4031. Although these studies suggested that clinically used synthetic estrogens with similar structures have the marked potential to alter hERG functions, the hERG interactions with synthetic estrogens have not been assessed. We therefore examined whether ethinylestradiol (EE2), a synthetic estrogen used in oral contraceptives, affects hERG function and blockade by drugs. Supratherapeutic concentrations of EE2 did not alter amplitudes or kinetics of the hERG currents elicited by train pulses at 20 mV (0.1 Hz). On the other hand, EE2 at therapeutic concentrations reduced the degree of hERG current suppression by E-4031. The administration of EE2 followed by E-4031 blockade reversed the current suppression, suggesting that the interaction of EE2 and E-4031 alters hERG at the drug-binding site. The effects of EE2 on hERG blockade raised the possibility that other estrogens, including synthetic estrogens, can alter hERG blockade by drugs that cause QT prolongation and ventricular arrhythmias. View Full-Text
Keywords: cardiac potassium channel; hERG blocker; synthetic estrogen; QT intervals; drug interaction cardiac potassium channel; hERG blocker; synthetic estrogen; QT intervals; drug interaction
Show Figures

Figure 1

MDPI and ACS Style

Tamura, F.; Sugimoto, S.; Sugimoto, M.; Sakamoto, K.; Yamaguchi, M.; Suzuki, T.; Fukuda, K.; Ieda, M.; Kurokawa, J. The Effect of a Synthetic Estrogen, Ethinylestradiol, on the hERG Block by E-4031. Biomolecules 2021, 11, 1385. https://doi.org/10.3390/biom11091385

AMA Style

Tamura F, Sugimoto S, Sugimoto M, Sakamoto K, Yamaguchi M, Suzuki T, Fukuda K, Ieda M, Kurokawa J. The Effect of a Synthetic Estrogen, Ethinylestradiol, on the hERG Block by E-4031. Biomolecules. 2021; 11(9):1385. https://doi.org/10.3390/biom11091385

Chicago/Turabian Style

Tamura, Fumiya, Shintaro Sugimoto, Mana Sugimoto, Kazuho Sakamoto, Masahiko Yamaguchi, Takeshi Suzuki, Keiichi Fukuda, Masaki Ieda, and Junko Kurokawa. 2021. "The Effect of a Synthetic Estrogen, Ethinylestradiol, on the hERG Block by E-4031" Biomolecules 11, no. 9: 1385. https://doi.org/10.3390/biom11091385

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop