Fluorescence-tracking of activation gating in human ERG channels reveals rapid S4 movement and slow pore opening.

ABSTRACT:

Background

hERG channels are physiologically important ion channels which mediate cardiac repolarization as a result of their unusual gating properties. These are very slow activation compared with other mammalian voltage-gated potassium channels, and extremely rapid inactivation. The mechanism of slow activation is not well understood and is investigated here using fluorescence as a direct measure of S4 movement and pore opening.

Methods and findings

Tetramethylrhodamine-5-maleimide (TMRM) fluorescence at E519 has been used to track S4 voltage sensor movement, and channel opening and closing in hERG channels. Endogenous cysteines (C445 and C449) in the S1-S2 linker bound TMRM, which caused a 10 mV hyperpolarization of the V((1/2)) of activation to -27.5+/-2.0 mV, and showed

SUBMITTER: Es-Salah-Lamoureux Z 

PROVIDER: S-EPMC2878317 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature