Dronedarone Blockage of the Tumor-related Kv10.1 Channel: a Comparison with Amiodarone

Overview

Journal Pflugers Arch

Specialty Physiology

Date 2020 Jan 4

PMID 31897736

Citations 2

Authors

T A Melendez

A Huanosta-Gutierrez

C Barriga-Montoya

M Gonzalez-Andrade

F Gomez-Lagunas

Affiliations

Soon will be listed here.

Abstract

Kv10.1 (Eag1, or KCNH1) is a human potassium-selective channel associated with tumor development. In this work, we study the interaction of the drug dronedarone with Kv10.1. Dronedarone presents two chemical modifications aimed to lessen side effects produced by its parent molecule, the antiarrhythmic amiodarone. Hence, our observations are discussed within the framework of a previously reported interaction of amiodarone with Kv10.1. Additionally, we show new data regarding the interaction of amiodarone with the channels. We found that, unexpectedly, the effect of dronedarone on Kv10.1 differs both quantitatively and qualitatively to that of amiodarone. Among other observations, we found that dronedarone seems to be an open-pore blocker, in contrast to the reported behavior of amiodarone, which seems to inhibit from both open and closed states. Additionally, herein we provide evidence showing that, in spite of their chemical similarity, these molecules inhibit the K conductance by binding to non-overlapping, independent (non-allosterically related) sites. Also, we show that, while amiodarone inhibits the Cole-Moore shift, dronedarone is unable to inhibit this voltage-dependent characteristic of Kv10.1.

Citing Articles

State-independent inhibition of the oncogenic Kv10.1 channel by desethylamiodarone, a comparison with amiodarone.

Gomez-Lagunas F, Barriga-Montoya C, Pardo J Pflugers Arch. 2023; 476(3):323-335.

PMID: 38063872 PMC: 10847070. DOI: 10.1007/s00424-023-02893-x.

Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.

Capatina A, Lagos D, Brackenbury W Rev Physiol Biochem Pharmacol. 2020; 183:1-43.

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