Expression and functional characterization of the human ether-a-go-go-related gene (HERG) K+ channel cardiac splice variant in Xenopus laevis oocytes

HERG C-Cardiac, a C-terminal splice variant of the human ether-a-go-go-related gene (HERG A), was identified and found to be 100% homologous to HERG(USO). Real-time polymerase chain reaction data indicated that in the human heart HERG C-Cardiac mRNA was expressed eight times more than HERG A, whereas in human ventricular tissue it was expressed six times more than HERG A. A HERG C-Cardiac-green fluorescence protein (GFP) construct was heterologously expressed in Xenopus oocytes. Confocal micrographs revealed that HERG C-Cardiac was mainly expressed in the plasma membrane. HERG C-Cardiac channel expressed in oocytes produced slower inactivating outward currents and faster deactivating tail currents than those of HERG A channel. Equal amounts of HERG A and HERG C-Cardiac cRNA coinjected into oocytes formed intermediate HERG A + HERG C-Cardiac heteromultimers, which was reconfirmed by immunoprecipitation experiments with a HERG A N-terminal antibody. These heteromultimers had different inactivation, deactivation and activation kinetics from those of HERG A and HERG C-Cardiac channels. HERG A + HERG C-Cardiac heteromultimers significantly reduced the model action potential mean amplitude and increased the fast and slow inactivation tau values of the action potential repolarization phase, suggesting involvement of HERG A and HERG C-Cardiac heteromultimers in modulation of the refractory interval.