Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
The slowly activating delayed-rectifier K+ current, I(Ks), modulates the repolarization of cardiac action potentials. The molecular structure of the I(Ks) channel is not known, but physiological data indicate that one component of the I(Ks), channel is minK, a 130-amino-acid protein with a single putative transmembrane domain. The size and structure of this protein is such that it is unlikely that minK alone forms functional channels. We have previously used positional cloning techniques to define a new putative K+-channel gene, KVLQT1. Mutations in this gene cause long-QT syndrome, an inherited disorder that increases the risk of sudden death from cardiac arrhythmias. Here we show that KVLQT1 encodes a K+ channel with biophysical properties unlike other known cardiac currents. We considered that K(V)LQT1 might coassemble with another subunit to form functional channels in cardiac myocytes. Coexpression of K(V)LQT1 with minK induced a current that was almost identical to cardiac I(Ks). Therefore, K(V)LQT1 is the subunit that coassembles with minK to form I(Ks) channels and I(Ks) dysfunction is a cause of cardiac arrhythmia.
Department of Medicine, Cardiology Division, University of Utah, Salt Lake City 84112, USA. mike.sanguinetti@genetics.utah.edu
M C
MC
Sanguinetti
M E
ME
Curran
A
A
Zou
J
J
Shen
P S
PS
Spector
D L
DL
Atkinson
M T
MT
Keating
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006224:Cricetinae; D018076:DNA, Complementary; D004594:Electrophysiology; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D009865:Oocytes; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014981:Xenopus
D018076:DNA, Complementary; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; C059983:potassium channel protein I(sk)