Jiang Min, Zhang Mei, Tang Daniel G, Clemo Henry F, Liu Jie, Holwitt Dana, Kasirajan Vigneshwar, Pond Amber L, Wettwer Erich, Tseng Gea-Ny
Department of Physiology, Virginia Commonwealth UniversityRichmond, VA 23298, USA.
Circulation. 2004 Apr 13;109(14):1783-8. doi: 10.1161/01.CIR.0000124225.43852.50. Epub 2004 Apr 5.
Mutations in KCNE2 have been linked to long-QT syndrome (LQT6), yet KCNE2 protein expression in the ventricle and its functional role in native channels are not clear.
We detected KCNE2 protein in human, dog, and rat ventricles in Western blot experiments. Immunocytochemistry confirmed KCNE2 protein expression in ventricular myocytes. To explore the functional role of KCNE2, we studied how its expression was altered in 2 models of cardiac pathology and whether these alterations could help explain observed changes in the function of native channels, for which KCNE2 is a putative auxiliary (beta) subunit. In canine ventricle injured by coronary microembolizations, the rapid delayed rectifier current (I(Kr)) density was increased. Although the protein level of ERG (I(Kr) pore-forming, alpha, subunit) was not altered, the KCNE2 protein level was markedly reduced. These data are consistent with the effect of heterologously expressed KCNE2 on ERG and suggest that in canine ventricle, KCNE2 may associate with ERG and suppress its current amplitude. In aging rat ventricle, the pacemaker current (I(f)) density was increased. There was a significant increase in the KCNE2 protein level, whereas changes in the alpha-subunit (HCN2) were not significant. These data are consistent with the effect of heterologously expressed KCNE2 on HCN2 and suggest that in aging rat ventricle, KCNE2 may associate with HCN2 and enhance its current amplitude.
KCNE2 protein is expressed in ventricles, and it can play diverse roles in ventricular electrical activity under (patho)physiological conditions.
KCNE2基因突变与长QT综合征（LQT6）相关，但KCNE2蛋白在心室中的表达及其在天然通道中的功能作用尚不清楚。
我们通过蛋白质印迹实验在人、犬和大鼠的心室中检测到了KCNE2蛋白。免疫细胞化学证实了KCNE2蛋白在心室肌细胞中的表达。为了探究KCNE2的功能作用，我们研究了在两种心脏病理模型中其表达如何改变，以及这些改变是否有助于解释天然通道功能的观察变化，KCNE2是这些天然通道假定的辅助（β）亚基。在冠状动脉微栓塞损伤的犬心室中，快速延迟整流电流（I(Kr)）密度增加。虽然ERG（I(Kr)的成孔α亚基）的蛋白水平未改变，但KCNE2蛋白水平显著降低。这些数据与异源表达的KCNE2对ERG的作用一致，表明在犬心室中，KCNE2可能与ERG结合并抑制其电流幅度。在衰老的大鼠心室中，起搏电流（I(f)）密度增加。KCNE2蛋白水平显著升高，而成孔α亚基（HCN2）的变化不显著。这些数据与异源表达的KCNE2对HCN2的作用一致，表明在衰老的大鼠心室中，KCNE2可能与HCN2结合并增强其电流幅度。
KCNE2蛋白在心室中表达，并且在（病理）生理条件下，它可在心室电活动中发挥多种作用。
