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Article

Biophysical Characterization of Epigallocatechin-3-Gallate Effect on the Cardiac Sodium Channel Nav1.5

1
R.N.E Laboratory, Multidisciplinary Faculty of Taza, University Sidi Mohamed Ben Abdellah of Fez, Fez 30000, Morocco
2
Science for Life Laboratory, Department of Applied Physics, KTH Royal Institute of Technology, SE-100 44 Solna, Sweden
3
Institute of Biochemistry and Molecular Medicine (IBMM), University of Bern, 3012 Bern, Switzerland
*
Authors to whom correspondence should be addressed.
Academic Editors: Saverio Bettuzzi and Jean-Marc Sabatier
Molecules 2020, 25(4), 902; https://doi.org/10.3390/molecules25040902
Received: 26 December 2019 / Revised: 7 February 2020 / Accepted: 15 February 2020 / Published: 18 February 2020
(This article belongs to the Special Issue Catechins in Human Health)
Epigallocatechin-3-Gallate (EGCG) has been extensively studied for its protective effect against cardiovascular disorders. This effect has been attributed to its action on multiple molecular pathways and transmembrane proteins, including the cardiac Nav1.5 channels, which are inhibited in a dose-dependent manner. However, the molecular mechanism underlying this effect remains to be unveiled. To this aim, we have characterized the EGCG effect on Nav1.5 using electrophysiology and molecular dynamics (MD) simulations. EGCG superfusion induced a dose-dependent inhibition of Nav1.5 expressed in tsA201 cells, negatively shifted the steady-state inactivation curve, slowed the inactivation kinetics, and delayed the recovery from fast inactivation. However, EGCG had no effect on the voltage-dependence of activation and showed little use-dependent block on Nav1.5. Finally, MD simulations suggested that EGCG does not preferentially stay in the center of the bilayer, but that it spontaneously relocates to the membrane headgroup region. Moreover, no sign of spontaneous crossing from one leaflet to the other was observed, indicating a relatively large free energy barrier associated with EGCG transport across the membrane. These results indicate that EGCG may exert its biophysical effect via access to its binding site through the cell membrane or via a bilayer-mediated mechanism. View Full-Text
Keywords: EGCG; Nav1.5; cellular electrophysiology; molecular dynamics; ion channels EGCG; Nav1.5; cellular electrophysiology; molecular dynamics; ion channels
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MDPI and ACS Style

Amarouch, M.-Y.; Kurt, H.; Delemotte, L.; Abriel, H. Biophysical Characterization of Epigallocatechin-3-Gallate Effect on the Cardiac Sodium Channel Nav1.5. Molecules 2020, 25, 902. https://doi.org/10.3390/molecules25040902

AMA Style

Amarouch M-Y, Kurt H, Delemotte L, Abriel H. Biophysical Characterization of Epigallocatechin-3-Gallate Effect on the Cardiac Sodium Channel Nav1.5. Molecules. 2020; 25(4):902. https://doi.org/10.3390/molecules25040902

Chicago/Turabian Style

Amarouch, Mohamed-Yassine, Han Kurt, Lucie Delemotte, and Hugues Abriel. 2020. "Biophysical Characterization of Epigallocatechin-3-Gallate Effect on the Cardiac Sodium Channel Nav1.5" Molecules 25, no. 4: 902. https://doi.org/10.3390/molecules25040902

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