Cardiovasc Res. 2003 Nov 1;60(2):235-41.

Defective protein trafficking in hERG-associated hereditary long QT syndrome (LQT2): molecular mechanisms and restoration of intracellular protein processing.

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Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, D-69115 Heidelberg, Germany. dierk_thomas@med.uni-heidelberg.de

Abstract

Human hereditary long QT syndrome is a cardiac disease characterized by prolongation of the QT interval and increased susceptibility to ventricular arrhythmias and sudden cardiac death. Mutations in the human-ether-a-go-go-related gene (hERG), encoding the protein underlying the repolarizing cardiac I(Kr) potassium current, cause chromosome 7-linked long QT syndrome 2. Loss of function of mutant hERG channels may be caused by several mechanisms, including altered current kinetics, altered ion selectivity, or defective intracellular protein trafficking. Especially the latter category has become a focus of particular interest recently, because some of the mutant subunits display wild type current properties when normal trafficking is restored and channels are inserted in the cell membrane in vitro. This review summarizes the current knowledge on hERG channel trafficking under physiological and pathological conditions. In addition, therapeutic approaches to restore normal hERG trafficking in vitro and in vivo are discussed.

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Cited by 13 PubMed Central articles

Trafficking defect and proteasomal degradation contribute to the phenotype of a novel KCNH2 long QT syndrome mutation. [PLoS One. 2011]
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