Journal of Membrane Biology

, Volume 228, Issue 1, pp 1–14

Regulation of the Kv2.1 Potassium Channel by MinK and MiRP1

  • Zoe A. McCrossan
  • Torsten K. Roepke
  • Anthony Lewis
  • Gianina Panaghie
  • Geoffrey W. Abbott
Article

Abstract

Kv2.1 is a voltage-gated potassium (Kv) channel α-subunit expressed in mammalian heart and brain. MinK-related peptides (MiRPs), encoded by KCNE genes, are single–transmembrane domain ancillary subunits that form complexes with Kv channel α-subunits to modify their function. Mutations in human MinK (KCNE1) and MiRP1 (KCNE2) are associated with inherited and acquired forms of long QT syndrome (LQTS). Here, coimmunoprecipitations from rat heart tissue suggested that both MinK and MiRP1 form native cardiac complexes with Kv2.1. In whole-cell voltage-clamp studies of subunits expressed in CHO cells, rat MinK and MiRP1 reduced Kv2.1 current density three- and twofold, respectively; slowed Kv2.1 activation (at +60 mV) two- and threefold, respectively; and slowed Kv2.1 deactivation less than twofold. Human MinK slowed Kv2.1 activation 25%, while human MiRP1 slowed Kv2.1 activation and deactivation twofold. Inherited mutations in human MinK and MiRP1, previously associated with LQTS, were also evaluated. D76N–MinK and S74L–MinK reduced Kv2.1 current density (threefold and 40%, respectively) and slowed deactivation (60% and 80%, respectively). Compared to wild-type human MiRP1–Kv2.1 complexes, channels formed with M54T– or I57T–MiRP1 showed greatly slowed activation (tenfold and fivefold, respectively). The data broaden the potential roles of MinK and MiRP1 in cardiac physiology and support the possibility that inherited mutations in either subunit could contribute to cardiac arrhythmia by multiple mechanisms.

Keywords

Potassium channel Long QT syndrome KCNE1 KCNE2 

Abbreviations

ERG

ether-a-go-go related gene product

Kv channel

Voltage-gated potassium channel

MiRP

MinK-related peptide

TEA

Tetraethylammonium

TM

Transmembrane

Supplementary material

232_2009_9154_MOESM1_ESM.pdf (395 kb)
Supplementary material 1 (PDF 395 kb)

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Zoe A. McCrossan
    • 1
  • Torsten K. Roepke
    • 1
    • 2
  • Anthony Lewis
    • 1
  • Gianina Panaghie
    • 1
  • Geoffrey W. Abbott
    • 1
  1. 1.Greenberg Division of Cardiology, Departments of Medicine and PharmacologyWeill Medical College of Cornell UniversityNew YorkUSA
  2. 2.Charite Campus Berlin-Buch, Experimental and Clinical Research CenterFranz Volhard Clinic and HELIOS KlinikumBerlinGermany

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