A minK-HERG complex regulates the cardiac potassium current I(Kr).
MinK is a widely expressed protein of relative molecular mass approximately 15K that forms potassium channels by aggregation with other membrane proteins. MinK governs ion channel activation, regulation by second messengers, and the function and structure of the ion conduction pathway. Association of minK with a channel protein known as KvLQT1 produces a voltage-gated outward K+ current (I[sK]) resembling the slow cardiac repolarization current (I[Ks]). HERG, a human homologue of the ether-a-go-go gene of the fruitfly Drosophila melanogaster, encodes a protein that produces the rapidly activating cardiac delayed rectifier (I[Kr]). These two potassium currents, I(Ks) and I(Kr), provide the principal repolarizing currents in cardiac myocytes for the termination of action potentials. Although heterologously expressed HERG channels are largely indistinguishable from native cardiac I(Kr), a role for minK in this current is suggested by the diminished I(Kr) in an atrial tumour line subjected to minK antisense suppression. Here we show that HERG and minK form a stable complex, and that this heteromultimerization regulates I(Kr) activity. MinK, through the formation of heteromeric channel complexes, is thus central to the control of the heart rate and rhythm.
McDonald
T V
TV
Section of Molecular Cardiology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. mcdonald@aecom.yu.edu
Yu
Z
Z
Ming
Z
Z
Palma
E
E
Meyers
M B
MB
Wang
K W
KW
Goldstein
S A
SA
Fishman
G I
GI
D000818:Animals; D016466:CHO Cells; D027682:Cation Transport Proteins; D006224:Cricetinae; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D004594:Electrophysiology; D000939:Epitopes / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels; D006388:Hemagglutinins / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014162:Transfection; D014981:Xenopus
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D000939:Epitopes; D051638:Ether-A-Go-Go Potassium Channels; D006388:Hemagglutinins; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C059983:potassium channel protein I(sk)