抄録
It is well known that cardiac KCNQ1 channel assembles with KCNE1 β-subunit to generate the slow IKs current that plays a major role in repolarization of action potential. However, it is also plausible that other KCNE members (i.e. KCNE2-5) may interact with cardiac KCNQ1 to form K+ channels with different properties because they are also substantially expressed in hearts. Here, we investigated the potential roles of KCNE1, KCNE2 and KCNE3 in cardiac KCNQ1 channel function. Transfection of KCNE1 into CHO cells stably expressing KCNQ1 resulted in evocation of slowly activating outward current that resembles IKs, whereas expression of either KCNE2 or KCNE3 induced a constitutively active K+ current. When KCNE1 and KCNE2 were cotransfected, the cell displayed IKs-like current whose characteristics substantially differed from those of the KCNQ1/KCNE1 current. On the other hand, the cell expressing both KCNE1 and KCNE3 exhibited an ensemble of the KCNQ1/KCNE1 and KCNQ1/KCNE3 currents. These results suggest that both KCNE2 and KCNE3 can participate in regulation of KCNQ1 channel even in the presence of KCNE1. In guinea-pig cardiomyocytes, transfection of siRNA directed against KCNE1 or KCNE2 reduced the amplitude of IKs and prolonged the action potential duration (APD). On the other hand, knockdown of KCNE3 resulted in a prolongation of APD without changing IKs amplitude which suggests that KCNE3 contributes to the determination of APD independent of IKs modulation. Our data suggests that not only KCNE1 but also KCNE2 and KCNE3 may play a physiological role in cardiac repolarization. [J Physiol Sci. 2008;58 Suppl:S176]
