Coassembly of KVLQT1 and minK (IsK) proteins to form cardiac IKS potassium channel

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Abstract
THE slowly activating delayed-rectifier K+ current, IKS, modulates the repolarization of cardiac action potentials. The molecular structure of the IKS channel is not known, but physiological data indicate that one component of theIKSchannel is minK (refs 1–6), a 130-amino-acid protein with a single putative transmembrane domain7. The size and structure of this protein is such that it is unlikely that minK alone forms functional channels8,9. We have previously used positional cloning techniques to define a new putative K+-channel gene, KVLQT110. 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 KVLQT1 might coassemble with another subunit to form func-tional channels in cardiac myocytes. Coexpression of KVLQT1 with minK induced a current that was almost identical to cardiac IKS. Therefore, KVLQT1 is the subunit that coassembles with minK to form IKS channels and IKS dysfunction is a cause of cardiac arrhythmia.