HERG K+ channels: friend and foe.
The K+ channel encoded by the human ether-à-go-go related gene (HERG) is one of many ion channels that are crucial for normal action potential repolarization in cardiac myocytes. HERG encodes the pore-forming subunit of the rapid component of the delayed rectifier K+ channel, I(K(Vr)). HERG K+ channels are of considerable pharmaceutical interest as possible therapeutic targets for anti-arrhythmic agents and as the molecular target responsible for the cardiac toxicity of a wide range of pharmaceutical agents. Recent studies of the molecular basis of the promiscuity of HERG K+ channel drug binding has not only started to shed light on this tricky pharmaceutical problem but has also provided further insights into the structure and function of HERG K+ channels.
Vandenberg
J I
JI
Dept of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, UK CB2 1QW. jiv@mole.bio.cam.ac.uk
Walker
B D
BD
Campbell
T J
TJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D015221:Potassium Channels / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D013329:Structure-Activity Relationship; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
D000889:Anti-Arrhythmia Agents; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG