Kv11.1 channel subunit composition includes MinK and varies developmentally in mouse cardiac muscle

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 a subunit alternative splice variant, Kv11.1a, is more abundant in adult heart while the Kv11.1 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.