Does hERG coassemble with a beta subunit? Evidence for roles of MinK and MiRP1.
The voltage-gated potassium channel formed by hERG pore-forming alpha subunits generates the IKr cardiac potassium current, and is considered essential for human ventricular repolarization. What is not certain is whether human IKr channels contain ancillary subunits in vivo. Two chief contenders for this role are MinK (encoded by KCNE1) and MiRP1 (KCNE2). MinK and MiRP1 are single transmembrane domain peptides that can co-assemble with hERG in heterologous systems. MinK increases hERG currents by an unknown mechanism. MiRP1 alters hERG current density and gating, although no consensus has been reached as to the precise extent of these effects. Here we discuss key aspects of the debate surrounding the potential roles of MinK and MiRP1 in IKr: inconsistencies between reports of the effects of MiRP1 on hERG in vitro; association with long QT syndrome of inherited mutations in MinK and MiRP1; and a role for MiRP1 polymorphisms in acquired arrhythmia despite the apparent inability of MiRP1 to impinge upon the unique inner vestibule drug-binding site that dominates hERG pharmacology.
Anantharam
Arun
A
Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Abbott
Geoffrey W
GW
D000818:Animals; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D015640:Ion Channel Gating; D008133:Long QT Syndrome / Q000503:physiopathology*; D008564:Membrane Potentials; D009154:Mutation; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C489622:KCNE1 protein, human; C489619:KCNE2 protein, human; C502068:KCNE5 protein, human; C000606913:KCNH2 protein, human; D024642:Potassium Channels, Voltage-Gated