Structural Basis forEther-a-go-go-Related Gene K+Channel Subtype-Dependent Activation by Niflumic Acid

Structural basis for ether-a-go-go-related gene K+ channel subtype-dependent activation by niflumic acid.

Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridinecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K(+) channel subtypes expressed in Xenopus laevis oocytes using two-electrode voltage-clamp tec...

Structural requirements of human ether-a-go-go-related gene channels for block by bupivacaine.

BACKGROUND Local anesthetics interact with human ether-a-go-go-related gene (HERG) channels via the aromatic amino acids Y652 and F656 in the S6 region. This study aimed to establish whether the residues T623, S624, and V625 residing deeper within the pore are also involved in HERG channel block by bupivacaine. In addition, the study aimed to further define the role of the aromatic residues Y65...

Structural basis of action for a human ether-a-go-go-related gene 1 potassium channel activator.

Activation of human ether-a-go-go-related gene 1 (hERG1) K(+) channels mediates cardiac action potential repolarization. Drugs that activate hERG1 channels represent a mechanism-based approach for the treatment of long QT syndrome, a disorder of cardiac repolarization associated with ventricular arrhythmia and sudden death. Here, we characterize the mechanisms of action and the molecular determ...

Regional specificity of human ether-a'-go-go-related gene channel activation and inactivation gating.

Slow activation and rapid C-type inactivation produce inward rectification of the current-voltage relationship for human ether-a'-go-go-related gene (hERG) channels. To characterize the voltage sensor movement associated with hERG activation and inactivation, we performed an Ala scan of the 32 amino acids (Gly(514)-Tyr(545)) that comprise the S4 domain and the flanking S3-S4 and S4-S5 linkers. ...

Calpain Activation by ROS mediates Human ether - a - go - go - related gene 2 Protein Degradation by Intermittent Hypoxia