Aydar Ebru, Palmer Christpher
Division of Cell and Molecular Biology, Imperial College, London, South Kensington Campus, Sir Alexander Fleming Building, London, UK.
J Membr Biol. 2006;211(2):115-26. doi: 10.1007/s00232-006-0010-9. Epub 2006 Oct 14.
HERG C(Cardiac), a C-terminal splice variant of the human ether-à-go-go-related gene (HERG A), was identified and found to be 100% homologous to HERG(USO). Real-time polymerase chain reaction data indicated that in the human heart HERG C(Cardiac )mRNA was expressed eight times more than HERG A, whereas in human ventricular tissue it was expressed six times more than HERG A. A HERG C(Cardiac)-green fluorescence protein (GFP) construct was heterologously expressed in Xenopus oocytes. Confocal micrographs revealed that HERG C(Cardiac )was mainly expressed in the plasma membrane. HERG C(Cardiac) channel expressed in oocytes produced slower inactivating outward currents and faster deactivating tail currents than those of HERG A channel. Equal amounts of HERG A and HERG C(Cardiac) cRNA coinjected into oocytes formed intermediate HERG A + HERG C(Cardiac) heteromultimers, which was reconfirmed by immunoprecipitation experiments with a HERG A N-terminal antibody. These heteromultimers had different inactivation, deactivation and activation kinetics from those of HERG A and HERG C(Cardiac) channels. HERG A + HERG C(Cardiac) heteromultimers significantly reduced the model action potential mean amplitude and increased the fast and slow inactivation tau values of the action potential repolarization phase, suggesting involvement of HERG A and HERG C(Cardiac) heteromultimers in modulation of the refractory interval.
人去极化相关基因（HERG A）的C末端剪接变体HERG C（心脏型）被鉴定出来，发现其与HERG（USO）具有100%的同源性。实时聚合酶链反应数据表明，在人的心脏中，HERG C（心脏型）mRNA的表达量是HERG A的8倍，而在人的心室组织中，其表达量是HERG A的6倍。一种HERG C（心脏型）-绿色荧光蛋白（GFP）构建体在非洲爪蟾卵母细胞中进行了异源表达。共聚焦显微镜图像显示，HERG C（心脏型）主要表达于质膜。卵母细胞中表达的HERG C（心脏型）通道产生的外向电流失活较慢，尾电流去激活较快，而HERG A通道则相反。等量的HERG A和HERG C（心脏型）cRNA共同注射到卵母细胞中形成了中间型HERG A + HERG C（心脏型）异源多聚体，用HERG A N末端抗体进行免疫沉淀实验再次证实了这一点。这些异源多聚体的失活、去激活和激活动力学与HERG A和HERG C（心脏型）通道不同。HERG A + HERG C（心脏型）异源多聚体显著降低了模型动作电位的平均幅度，并增加了动作电位复极化阶段的快速和慢速失活时间常数，提示HERG A和HERG C（心脏型）异源多聚体参与了不应期的调节。
