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KvLQT1 and IsK (minK) proteins associate to form the IKS cardiac potassium current


IN mammalian cardiac cells, a variety of transient or sustained K+ currents contribute to the repolarization of action potentials1. There are two main components of the delayed-rectifier sustained K+ current, IKr (rapid) and IKS (slow)2. IKr is the product of the gene HERG3,4 which is altered in the long-QT syndrome, LQT2 (ref. 5). A channel with properties similar to those of the IKS channel is produced when the cardiac protein IsK is expressed in Xenopus oocytes6–8. However, it is a small protein with a very unusual structure for a cation channel9–15. The LQT1 gene is another gene associated with the LQT syndrome, a disorder that causes sudden death from ventricular arrhythmias16. Here we report the cloning of the full-length mouse KVLQT1 complemen-tary DNA and show that KVLQT1 associates with IsK to form the channel underlying the IKS cardiac current, which is a target of class-Ill anti-arrhythmic drugs and is involved in the LQT1 syndrome.

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Barhanin, J., Lesage, F., Guillemare, E. et al. KvLQT1 and IsK (minK) proteins associate to form the IKS cardiac potassium current. Nature 384, 78–80 (1996).

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