Inhibition of the K+ conductance and Cole-Moore shift of the oncogenic Kv10.1 channel by amiodarone

Abstract

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.

Potassium channels: Novel targets for tumor diagnosis and chemoresistance

“…Kv10.1 is a standard tumor marker that is overexpressed in approximately 70% of human tumors and cancer cell lines, and channel inhibition reduces tumor growth ( 70 ). Chloroquine, as a Kv10.1 channel inhibitor, can inhibit outward potassium currents in BC cells, thereby reducing cell migration ( 71 ).…”