KCNE2 confers background current characteristics to the cardiac KCNQ1 potassium channel

Mutations in HERG and KCNQ1 (or KVLQT1) genes cause the life-threatening Lo ng QT syndrome. These genes encode K+ channel pore-forming subunits that as sociate with ancillary subunits from the KCNE family to underlie the two co mponents, I-Kr and I-Ks, of the human cardiac delayed rectifier current I-K . The KCNE family comprises at least three members. KCNE1 (IsK or MinK) rec apitulates I-Ks, when associated with KCNQ1, whereas it augments the amplit ude of an I-Kr-like current when co-expressed with HERG, KCNE3 markedly cha nges KCNQ1 as well as HERG current properties. So far, KCNE2 (MirP1) has on ly been shown to modulate HERG current, Here we demonstrate the interaction of KCNE2 with the KCNQ1 subunit, which results in a drastic change of KCNQ 1 current amplitude and gating properties. Furthermore, KCNE2 mutations als o reveal their specific functional consequences on KCNQ1 currents. KCNQ1 an d HERG appear to share unique interactions with KCNE1, 2 and 3 subunits, Wi th the exception of KCNE3, mutations in all these partner subunits have bee n found to lead to an increased propensity for cardiac arrhythmias.