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 α 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 α 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.