Pond A L, Nerbonne J M
Department of Basic Medical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Trends Cardiovasc Med. 2001 Oct;11(7):286-94. doi: 10.1016/s1050-1738(01)00127-x.
The voltage-gated K(+) channel (Kv) pore forming alpha subunit, ERG1 (KCNH2), has been identified as the locus of mutations in one type of inherited long QT syndrome, LQT2. Heterologous expression of ERG1 reveals rapidly activating and inactivating K(+) currents, characterized by marked inward rectification at potentials positive to 0 mV, which are similar to the rapid component of cardiac delayed rectification I(Kr). There are, however, marked differences in the properties of expressed ERG1 and endogenous cardiac I(Kr), suggesting that functional I(Kr) channels reflect the coassembly of full-length ERG1 with splice variants and /or accessory subunits. Consistent with these hypotheses, N- and C-terminal variants of ERG1 have been identified, and it has been demonstrated that heterologously expressed ERG1 and minK (or MiRP1) coimmunoprecipitate. Recent biochemical studies, however, suggest that only full-length ERG1 is expressed in adult mouse, rat, or human heart. Clearly, further studies, focused on identifying the subunits that coassemble with ERG1 in vivo, as well as on post-translational processing of the full-length ERG1 protein will be necessary to define the molecular composition of functional cardiac I(Kr) channels.
电压门控钾离子通道（Kv）的孔形成α亚基ERG1（KCNH2）已被确定为一种遗传性长QT综合征（LQT2）的突变位点。ERG1的异源表达显示出快速激活和失活的钾离子电流，其特征是在正于0 mV的电位下有明显的内向整流，这与心脏延迟整流I(Kr)的快速成分相似。然而，表达的ERG1和内源性心脏I(Kr)的特性存在明显差异，这表明功能性I(Kr)通道反映了全长ERG1与剪接变体和/或辅助亚基的共同组装。与这些假设一致，已鉴定出ERG1的N端和C端变体，并且已证明异源表达的ERG1和minK（或MiRP1）可共同免疫沉淀。然而，最近的生化研究表明，在成年小鼠、大鼠或人类心脏中仅表达全长ERG1。显然，需要进一步开展研究，重点是确定在体内与ERG1共同组装的亚基，以及全长ERG1蛋白的翻译后加工，以确定功能性心脏I(Kr)通道的分子组成。
