The inward rectification mechanism of the HERG cardiac potassium channel.
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.
Smith
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PL
Department of Neurobiology, Harvard Medical School, Boston, MA 02114-2698, USA.
Baukrowitz
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Yellen
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D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D027682:Cation Transport Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins; D004330:Drosophila; D029721:Drosophila Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D015640:Ion Channel Gating; D008133:Long QT Syndrome / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D051637:Shaker Superfamily of Potassium Channels; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; C496929:Sh protein, Drosophila; D051637:Shaker Superfamily of Potassium Channels; D013757:Tetraethylammonium Compounds; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D019789:Tetraethylammonium; D008274:Magnesium