Dronedarone blockage of the tumor-related Kv10.1 channel: a comparison with amiodarone
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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.
KeywordsPotassium channels Kv10.1 Eag1 Dronedarone Amiodarone Cole-Moore shift
Authors want to thank Mrs. Josefina Bolado, Head of the Scientific Paper Translation Department, from División de Investigación at Facultad de Medicina, UNAM, for editing the English-language version of this manuscript.
TAM, CBM, and AHR made experiments and analyzed results; MGA analyzed results and discussed the article; and FGL designed the research, made experiments, analyzed results and wrote the article.
This research was supported by PAPIIT grant IN219918. TAM is a doctoral student from Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), and is supported by CONACYT (#450763). AHG is a DGAPA-UNAM postdoctoral fellow.
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Conflict of interest
The authors declare that they have no conflicts of interest.
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