Finley Melissa R, Li Yan, Hua Fei, Lillich James, Mitchell Kathy E, Ganta Suhasini, Gilmour Robert F, Freeman Lisa C
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506-5802, USA.
Am J Physiol Heart Circ Physiol. 2002 Jul;283(1):H126-38. doi: 10.1152/ajpheart.00622.2001.
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.
在犬类和人类中，由醚 - 去极化相关基因1蛋白ERG1（KCNH2）和KCNQ1α亚基与KCNEβ亚基共同形成的钾通道，在正常复极化过程中发挥作用，并且可能与长QT综合征（LQTS）相关的异常复极化有关。尽管马会出现常见的心律失常，并且可能会接受诱发LQTS的药物，但马心脏复极化的分子基础尚不清楚。在马心脏中，我们使用免疫印迹和免疫染色来证明ERG1、KCNQ1、KCNE1和KCNE3蛋白的表达，并使用RT-PCR检测KCNE2信息。检测到了肽N - 糖苷酶F敏感形式的马ERG1（145 kDa）和KCNQ1（75 kDa）。ERG1和KCNQ1都与KCNE1进行了共免疫沉淀。ERG1拮抗剂（MK - 499、西沙必利）或KCNQ1/KCNE1拮抗剂（色满醇293B）均可延长心脏动作电位时程。膜片钳分析证实存在缓慢延迟整流电流。这些数据表明，马的复极电流与其他物种相似，因此马有获得性LQTS的风险。这些数据还为心脏组织中ERG1和KCNE1之间的共关联提供了独特的证据。
