K(v)LQT1 and IsK (minK) proteins associate to form the I-Ks cardiac potassium current

IN mammalian cardiac cells, a varlets of transient or sustained K+ currents contribute to the repolarization of action potentials(1). There are two main components of the delayed-rectifier sustained K+ current, I-Kr (rapid) and I-Ks (slow)(2). I-Kr is the product of the gene HERG(3,4), which is altered in the long-QT syndrome, LQT2 (ref. 5). A channel with properties similar to those of the I-Ks channel is produced when the cardiac protein IsK is expressed in Xenopus oocytes(6-8). However, it is a small protein with a very unusual structure for a cation channel(9-15). The LQT1 gene is another gene associated with the LQT syndrome, a disorder that causes sudden death from ventricular arrhythmias(16). Here we report the cloning of the full-length mouse K(v)LQT1 complementary DNA and show that K(v)LQT1 associates with IsK to form the channel underlying the I-Ks cardiac current, which is a target of class-III anti-arrhythmic drugs and is involved in the LQT(1) syndrome.