The transient receptor potential melastatin 4 channel inhibitor 9-phenanthrol modulates cardiac sodium channel

British Journal of Pharmacology
Jian-Wen HouYi-Gang Li

Abstract

9-Phenanthrol, known as a specific inhibitor of the transient receptor potential melastatin 4 (TRMP4) channel, has been shown to modulate cardiac electrical activity and exert antiarrhythmic effects. However, its pharmacological effects remain to be fully explored. Here, we tested the hypothesis that cardiac sodium current inhibition contributes to the cardioprotective effect of 9-phenanthrol. Single ventricular myocytes (VMs) and Purkinje cells (PCs) were enzymatically isolated from rabbits. Arterially perfused rabbit wedge preparations were also used, and transmural electrocardiogram and endocardial action potentials (APs) were simultaneously recorded. Wild-type and mutated human recombinant SCN5A were expressed in HEK293 cells. Anemonia toxin II (ATX-II) was used to amplify the late sodium current (INaL ) and induce arrhythmias. Whole-cell patch clamp technique was used to record APs and ionic currents. 9-Phenanthrol (10-50 μM) stabilized ventricular repolarization and abolished arrhythmias induced by ATX-II in both isolated VMs, PCs and wedge preparations. Further study revealed that 9-phenanthrol modulated the gating properties of cardiac sodium channels and dose-dependently inhibited INaL and peak sodium current (INaP ) i...Continue Reading

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Jun 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Khadija BelasriIstván Szatmári
Apr 4, 2021·International Journal of Molecular Sciences·Lijo Cherian OzhathilHugues Abriel

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