MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia.

Article Details

Citation

Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA

MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia.

Cell. 1999 Apr 16;97(2):175-87.

PubMed ID
10219239 [ View in PubMed
]
Abstract

A novel potassium channel gene has been cloned, characterized, and associated with cardiac arrhythmia. The gene encodes MinK-related peptide 1 (MiRP1), a small integral membrane subunit that assembles with HERG, a pore-forming protein, to alter its function. Unlike channels formed only with HERG, mixed complexes resemble native cardiac IKr channels in their gating, unitary conductance, regulation by potassium, and distinctive biphasic inhibition by the class III antiarrhythmic E-4031. Three missense mutations associated with long QT syndrome and ventricular fibrillation are identified in the gene for MiRP1. Mutants form channels that open slowly and close rapidly, thereby diminishing potassium currents. One variant, associated with clarithromycin-induced arrhythmia, increases channel blockade by the antibiotic. A mechanism for acquired arrhythmia is revealed: genetically based reduction in potassium currents that remains clinically silent until combined with additional stressors.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Potassium voltage-gated channel subfamily H member 2Q12809Details
Potassium voltage-gated channel subfamily E member 2Q9Y6J6Details
Pharmaco-genomics
DrugInteracting Gene/EnzymeAllele nameGenotypesDefining change(s)Type(s)DescriptionDetails
AmiodaronePotassium voltage-gated channel subfamily H member 2
Gene symbol: KCNH2
UniProt: Q12809
MiRP1Not Available
  • KCNE2
ADR Directly StudiedThe presence of polymorphisms in KCNH2 and KCNE2 may potentially be associated with increased susceptibility to long Q-T syndrome or cardiac arrhytmia when treated with amiodarone.Details