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 th e repolarization or cardiac action potentials. The molecular structure of the I-Ks, channel is not known, but physiological data indicate th at one component of the I-Ks channel is minK (refs 1-6), a 130-amino-a cid protein with a single putative transmembrane domain(7). The size a nd structure of this protein is such that it is unlikely that minK alo ne forms functional channels(8,9). We have previously used positional cloning techniques to define a new putative K+-channel gene, KVLQT1(10 ). Mutations in this gene cause long-QT syndrome, an inherited disorde r that increases the risk of sudden death from cardiac arrhythmias. He re se show that KVLQT1 encodes a K+ channel with biophysical propertie s unlike other known cardiac currents. We considered that K(v)LQT1 mig ht coassemble with another subunit to form functional channels in card iac myocytes. Coexpression of K(v)LQT1 with minK induced a current tha t was almost identical to cardiac I-Ks. Therefore, K(v)LQT1 is the sub unit that coassembles with minK to form I-Ks channels and I-Ks dysfunc tion is a cause of cardiac arrhythmia.