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Barriga-Montoya, C; Huanosta-Gutierrez, A; Reyes-Vaca, A; Hernandez-Cruz, A; Picones, A; Gomez-Lagunas, F (2018)

INHIBITION OF THE K+ CONDUCTANCE AND COLE-MOORE SHIFT OF THE ONCOGENIC KV10.1 CHANNEL BY AMIODARONE

Pflugers Arch. 470(3):491-503
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The ectopic overexpression of the voltage-dependent Eag1 (Kv10.1) Kchannel 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.