Inhibition of the K+ conductance and Cole-Moore shift of the oncogenic Kv10.1 channel by amiodarone
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The ectopic overexpression of the voltage-dependent Eag1 (Kv10.1) K+ channel is associated with the cancerous phenotype in about 70% of human cancers and tumor cell lines. Recent reports showed that, compared with the canonical Shaker-related Kv family, Kv10.1 presents unique structural and functional properties. Herein, we report the interaction of the class III anti-arrhythmic compound amiodarone with Kv10.1. Using whole-cell patch clamp, we found that amiodarone inhibits Kv10.1 channel conductance with nanomolar affinity. Additionally, and interestingly, we also report that amiodarone inhibits the characteristic Cole-Moore shift of Eag1 channels. Our observations are interpreted considering the structural-functional characteristics of these channels. We conclude that amiodarone possibly binds with high affinity to the voltage sensor module, altering the gating of Kv10.1.
KeywordsEag channels Kv10.1 Cole-Moore shift Amiodarone Pharmacology Cancer
The authors thank Dr. Daniel Balleza for his participation in the initial phase of this work and to Mrs. Josefina Bolado of the School of Medicine, UNAM, for reviewing the English language of the manuscript.
CBM, AHG ARV, AHC, and AP made experiments and contributed to the analysis of results; FGL designed the work, made experiments, analyzed results and wrote the article.
This research was supported by PAPIIT grants IN22461-RN22461 and IN219918 grants from CONACyT Laboratorios Nacionales Consolidaci461-RN224616, for reviewin05 and 153504, and PAPIIT IN211616 and IN220916. 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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