European Biophysics Journal

, Volume 38, Issue 5, pp 569–576 | Cite as

Role of intracellular domains in the function of the herg potassium channel

Original Paper

Abstract

The functional role of the large intracellular regions (which include the cyclic nucleotide binding domain, cNBD, and the Per-Arnt-Sim domain, PAS) in the herg channel is not well understood. We have studied possible interactions of the cNBD with other parts of the channel protein using lysine mutations to disrupt such interactions. Some lysine mutations caused significant right shifts in the voltage dependence of inactivation; almost all the mutants caused speeding up of deactivation time course. In a homology model of the cNBD, lysine mutations that affected both inactivation and deactivation lie in a hydrophobic band on the surface of the structure of this domain. Some known mutations in the Long QT Syndrome type 2, with effects on deactivation, are located at residues close to hydrophobic bands on the cNBD and the PAS domains. Such bands of residues in these intracellular domains may play an important part in channel function.

Keywords

Human ether-a-go-go-related gene Herg Cyclic nucleotide binding domain Potassium channel Electrophysiology 

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Copyright information

© European Biophysical Societies' Association 2009

Authors and Affiliations

  1. 1.Faculty of Biological SciencesUniversity of LeedsLeedsUK

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