Abstract
A human genetic defect associated with 'long Q-T syndrome', an abnormality of cardiac rhythm involving the repolarization of the action potential, was recently found to lie in the HERG gene, which codes for a potassium channel. The HERG K+ channel is unusual in that it seems to have the architectural plan of the depolarization-activated K+ channel family (six putative transmembrane segments), yet it exhibits rectification like that of the inward-rectifying K+ channels, a family with different molecular structure (two transmembrane segments). We have studied HERG channels expressed in mammalian cells and find that this inward rectification arises from a rapid and voltage-dependent inactivation process that reduces conductance at positive voltages. The inactivation gating mechanism resembles that of C-type inactivation, often considered to be the 'slow inactivation' mechanism of other K+ channels. The characteristics of this gating suggest a specific role for this channel in the normal suppression of arrhythmias.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Arrhythmias, Cardiac / metabolism
-
Cation Transport Proteins*
-
Cell Line
-
DNA-Binding Proteins*
-
Drosophila
-
Drosophila Proteins
-
ERG1 Potassium Channel
-
Ether-A-Go-Go Potassium Channels
-
Humans
-
Ion Channel Gating
-
Long QT Syndrome / metabolism
-
Magnesium / pharmacology
-
Membrane Potentials
-
Mutation
-
Myocardium / metabolism*
-
Potassium Channel Blockers
-
Potassium Channels / genetics
-
Potassium Channels / metabolism*
-
Potassium Channels, Voltage-Gated*
-
Recombinant Proteins
-
Shaker Superfamily of Potassium Channels
-
Tetraethylammonium
-
Tetraethylammonium Compounds / pharmacology
-
Trans-Activators*
-
Transcriptional Regulator ERG
Substances
-
Cation Transport Proteins
-
DNA-Binding Proteins
-
Drosophila Proteins
-
ERG protein, human
-
ERG1 Potassium Channel
-
Ether-A-Go-Go Potassium Channels
-
KCNH2 protein, human
-
KCNH6 protein, human
-
Potassium Channel Blockers
-
Potassium Channels
-
Potassium Channels, Voltage-Gated
-
Recombinant Proteins
-
Sh protein, Drosophila
-
Shaker Superfamily of Potassium Channels
-
Tetraethylammonium Compounds
-
Trans-Activators
-
Transcriptional Regulator ERG
-
Tetraethylammonium
-
Magnesium