HERG CCardiac, a C-terminal splice variant of the human ether-à-go-go-related gene (HERG A), was identified and found to be 100% homologous to HERGUSO. Real-time polymerase chain reaction data indicated that in the human heart HERG CCardiac 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 CCardiac-green fluorescence protein (GFP) construct was heterologously expressed in Xenopus oocytes. Confocal micrographs revealed that HERG CCardiac was mainly expressed in the plasma membrane. HERG CCardiac 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 CCardiac cRNA coinjected into oocytes formed intermediate HERG A + HERG CCardiac 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 CCardiac channels. HERG A + HERG CCardiac heteromultimers significantly reduced the model action potential mean amplitude and increased the fast and slow inactivation τ values of the action potential repolarization phase, suggesting involvement of HERG A and HERG CCardiac heteromultimers in modulation of the refractory interval.
The Journal of Membrane Biology – Springer Journals
Published: Oct 14, 2006
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