Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

101

33-POS

Board 33

Inhibition of the K

-Conductance and Cole-moore Shift of the Tumor Related Kv10.1

Channel by Amiodarone

Carolina Barriga-Montoya, Areli Huanosta-Gutiérrez, Arturo Reyes-Vaca, Arturo Hernández-

Cruz, Arturo Picones,

Froylán Gómez-Lagunas.

Universidad Nacional Autónoma de México, Ciudad de México, Mexico.

Ectopic overexpression of the voltage-dependent Eag1 (Kv10.1) K

channel is associated with

the cancerous phenotype of about 70% of human cancers and tumor cell lines. Recent reports

show 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. We found that amiodarone inhibits the K+-

conductance with nanomollar affinity. Additionally amiodarone inhibits the characteristic Cole-

Moore shift of Eag channels. Our observations are interpreted considering the recently reported

structure of the channel. We conclude that amiodarone binds both to the pore and voltage sensor

modules, including within the latter the cytoplasmic Per-Arnt-Sim-domain which is known to

regulate the voltage dependency of Kv10.1.