Wang Xun, Xu Rongzuo, Abernathey Grant, Taylor Jordan, Alzghoul M B, Hannon Kevin, Hockerman Gregory H, Pond Amber L
Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 47906, USA.
Dev Dyn. 2008 Sep;237(9):2430-7. doi: 10.1002/dvdy.21671.
The Kv11.1 (also ERG1) K(+) channel underlies cardiac I(Kr), a current that contributes to repolarization in mammalian heart. In mice, I(Kr) current density decreases with development and studies suggest that changes in the structure and/or properties of the heteromultimeric I(Kr)/Kv11.1 channel are responsible. Here, using immunohistochemistry, we report that total Kv11.1 alpha subunit protein is more abundant in neonatal heart and is distributed throughout both adult and neonatal ventricles with greater abundance in epicardia. Immunoblots reveal that the alpha subunit alternative splice variant, Kv11.1a, is more abundant in adult heart while the Kv11.1b variant is more abundant in neonatal heart. Additionally, MinK channel subunit protein is shown to co-assemble with Kv11.1 protein and is more abundant in neonatal heart. In summary, Kv11.1/I(Kr) channel composition varies developmentally and the higher I(Kr) current density in neonatal heart is likely attributable to higher abundance of Kv11.1/I(Kr) channels, more specifically, the Kv11.1b splice variant.
Kv11.1(也称为ERG1)钾通道是心脏I(Kr)电流的基础,该电流有助于哺乳动物心脏的复极化。在小鼠中,I(Kr)电流密度随发育而降低,研究表明异源多聚体I(Kr)/Kv11.1通道的结构和/或特性变化是其原因。在此,我们使用免疫组织化学报告,Kv11.1α亚基总蛋白在新生心脏中更为丰富,且分布于成年和新生心室中,在心外膜中含量更高。免疫印迹显示,α亚基可变剪接变体Kv11.1a在成年心脏中更为丰富,而Kv11.1b变体在新生心脏中更为丰富。此外,MinK通道亚基蛋白显示与Kv11.1蛋白共同组装,且在新生心脏中更为丰富。总之,Kv11.1/I(Kr)通道组成随发育而变化,新生心脏中较高的I(Kr)电流密度可能归因于Kv11.1/I(Kr)通道的丰度更高,更具体地说,是Kv11.1b剪接变体。