Targeted deletion of kcne2 impairs ventricular repolarization via disruption of IK,slow1 and Ito,f

Torsten K. Roepke, Andrianos Kontogeorgis, Christopher Ovanez, Xianghua Xu, Jeffrey B. Young, Kerry Purtell, Peter A. Goldstein, David J. Christini, Nicholas S. Peters, Fadi G. Akar, David E. Gutstein, Daniel J. Lerner, Geoffrey W. Abbott

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Mutations in human KCNE2, which encodes the MiRP1 potassium channel ancillary subunit, associate with long QT syndrome (LQTS), a defect in ventricular repolarization. The precise cardiac role of MiRP1 remains controversial, in part, because it has marked functional promiscuity in vitro. Here, we disrupted the murine kcne2 gene to define the role of MiRP1 in murine ventricles. kcne2 disruption prolonged ventricular action potential duration (APD), suggestive of reduced repolarization capacity. Accordingly, kcne2 (-/-) ventricles exhibited a 50% reduction in IK,slow1, generated by Kv1.5 - a previously unknown partner for MiRP1. Ito,f, generated by Kv4 α subunits, was also diminished, by ∼25%. Ventricular MiRP1 protein coimmunoprecipitated with native Kv1.5 and Kv4.2 but not Kv1.4 or Kv4.3. Unexpectedly, kcne2 (-/-) ventricular membrane fractions exhibited 50% less mature Kv1.5 protein than wild type, and disruption of Kv1.5 trafficking to the intercalated discs. Consistent with the reduction in ventricular K+ currents and prolonged ventricular APD, kcne2 deletion lengthened the QTc under sevoflurane anesthesia. Thus, targeted disruption of kcne2 has revealed a novel cardiac partner for MiRP1, a novel role for MiRPs in α subunit targeting in vivo, and a role for MiRP1 in murine ventricular repolarization with parallels to that proposed for the human heart.

Original languageEnglish (US)
Pages (from-to)3648-3660
Number of pages13
JournalFASEB Journal
Issue number10
StatePublished - Oct 2008
Externally publishedYes


  • Cardiac arrhythmia
  • Kv1.5
  • Kv4.2
  • Long QT syndrome
  • MiRP1
  • Potassium channel

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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