ICA-105574 interacts with a common binding site to elicit opposite effects on inactivation gating of EAG and ERG potassium channels.

ABSTRACT: Rapid and voltage-dependent inactivation greatly attenuates outward currents in ether-a-go-go-related gene (ERG) K(+) channels. In contrast, inactivation of related ether-a-go-go (EAG) K(+) channels is very slow and minimally reduces outward currents. ICA-105574 (ICA, or 3-nitro-N-[4-phenoxyphenyl]-benzamide) has opposite effects on inactivation of these two channel types. Although ICA greatly attenuates ERG inactivation by shifting its voltage dependence to more positive potentials, it enhances the rate and extent of EAG inactivation without altering its voltage dependence. Here, we investigate whether the inverse functional response to ICA in EAG and ERG channels is related to differences in ICA binding site or to intrinsic mechanisms of inactivation. Molecular modeling coupled with site

SUBMITTER: Garg V 

PROVIDER: S-EPMC3608434 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature