These authors contributed equally to this work.
Blockade of HERG K+ channel by an antihistamine drug brompheniramine requires the channel binding within the S6 residue Y652 and F656
Article first published online: 21 MAY 2007
Copyright © 2007 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 28, Issue 2, pages 104–111, March 2008
How to Cite
Park, S.-J., Kim, K.-S. and Kim, E.-J. (2008), Blockade of HERG K+ channel by an antihistamine drug brompheniramine requires the channel binding within the S6 residue Y652 and F656. J. Appl. Toxicol., 28: 104–111. doi: 10.1002/jat.1252
- Issue published online: 29 FEB 2008
- Article first published online: 21 MAY 2007
- Manuscript Accepted: 5 MAR 2007
- Manuscript Revised: 3 MAR 2007
- Manuscript Received: 22 JAN 2007
- HERG potassium channel;
- cardiac action potential duration;
- long QT syndrome;
A number of clinically used drugs block delayed rectifier K+ channels and prolong the duration of cardiac action potentials associated with long QT syndrome. This study investigated the molecular mechanisms of voltage-dependent inhibition of human ether-a-go-go-related gene (HERG) delayed rectifier K+ channels expressed in HEK-293 cells by brompheniramine, an antihistamine. Brompheniramine inhibited HERG current in a concentration-dependent manner with the half-maximal inhibitory concentration (IC50) value of 1.7 µm at 0 mV. A block of HERG current by brompheniramine was enhanced by progressive membrane depolarization and showed significantly negative shift in voltage-dependence of channel activation. Inhibition of HERG current by brompheniramine showed time-dependence. The S6 residue HERG mutant Y652A and F656C largely reduced the blocking potency of HERG current. These results indicate that brompheniramine mainly inhibited the HERG potassium channel through the residue Y652 and F656 and these residues may be an obligatory determinant in inhibition of HERG current for brompheniramine. Copyright © 2007 John Wiley & Sons, Ltd.