Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart
Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart
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DOI：
10.1152/ajpheart.00622.2001
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发表时间：
2002-07-01
影响因子：
4.8
通讯作者：
Freeman, LC
中科院分区：
文献类型：
--
作者：
Finley, MR;Li, Y;Freeman, LC
在狗和人中，由乙醚-a-GO-GO相关基因1蛋白ERG1(KCNH2)和KCNQ1α亚基形成的钾通道与KCNEβ亚基相关，在正常复极中发挥作用，并可能与长QT综合征(LQTS)相关的异常复极有关。马心脏复极的分子基础尚不清楚，尽管马表现出常见的心律失常，并可能接受诱导LQTS的药物。在马心中，我们用免疫印迹和免疫染色证明了ERG1、KCNQ1、KCNE1和KCNE3蛋白的表达，并用RT-PCR检测了KCNE2的信息。检测了马ERG1(145 KDa)和KCNQ1(75 KDa)的多肽N-糖苷酶F敏感形式。ERG1和KCNQ1均与KCNE1共沉淀。ERG1(MK-499，西沙必利)或KCNQ1/KCNE1(色满酚293B)拮抗剂均可延长心脏动作电位时程。膜片钳分析证实了缓慢延迟整流电流的存在。这些数据表明，马的复极电流与其他物种的复极电流相似，因此马面临获得性LQT的风险。这些数据也为ERG1和KCNE1在心脏组织中的相关性提供了独特的证据。
In dogs and in humans, potassium channels formed by ether-a-go-go-related gene 1 protein ERG1 (KCNH2) and KCNQ1 alpha-subunits, in association with KCNE beta-subunits, play a role in normal repolarization and may contribute to abnormal repolarization associated with long QT syndrome (LQTS). The molecular basis of repolarization in horse heart is unknown, although horses exhibit common cardiac arrhythmias and may receive drugs that induce LQTS. In horse heart, we have used immunoblotting and immunostaining to demonstrate the expression of ERG1, KCNQ1, KCNE1, and KCNE3 proteins and RT-PCR to detect KCNE2 message. Peptide N-glycosidase F-sensitive forms of horse ERG1 (145 kDa) and KCNQ1 (75 kDa) were detected. Both ERG1 and KCNQ1 coimmunoprecipitated with KCNE1. Cardiac action potential duration was prolonged by antagonists of either ERG1 (MK-499, cisapride) or KCNQ1/KCNE1 (chromanol 293B). Patch-clamp analysis confirmed the presence of a slow delayed rectifier current. These data suggest that repolarizing currents in horses are similar to those of other species, and that horses are therefore at risk for acquired LQTS. The data also provide unique evidence for coassociation between ERG1 and KCNE1 in cardiac tissue.