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Updated: May 21, 2026

Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes
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Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes

Published on: March 12, 2013

Long QT2 mutation on the Kv11.1 ion channel inhibits current activity by ablating a protein kinase Cα consensus site

Alexander J Donovan1, Katherine Lansu, Jason G Williams

  • 1Departments of Molecular Pharmacology and Therapeutics, Loyola University, Chicago, Illinois, USA.

Molecular Pharmacology
|June 2, 2012
PubMed

Insights

Mutations in the Kv11.1 ion channel cause long QT2 (LQT2) syndrome. This study reveals how a specific LQT2 mutation disrupts Kv11.1 channel function by affecting its phosphorylation by protein kinase C alpha (PKCα).

Area of Science:

  • Molecular biology
  • Cardiology
  • Ion channel physiology

Background:

  • Mutations in the Kv11.1 ion channel are linked to long QT2 (LQT2) syndrome, a condition causing cardiac arrhythmias and sudden death.
  • The precise molecular mechanisms underlying Kv11.1 malfunction in LQT2 remain largely unknown.
  • Disease-associated mutations can alter ion channel activity by affecting kinase consensus sites.

Purpose of the Study:

  • To investigate the molecular mechanism by which a LQT2-associated mutation affects Kv11.1 ion channel activity.
  • To determine the role of protein kinase C alpha (PKCα) and Ser890 phosphorylation in Kv11.1 channel function and LQT2 pathogenesis.

Main Methods:

  • Mass spectrometry to identify phosphorylation sites on Kv11.1.
  • Phospho-detection immunoassay and genetic manipulation to confirm PKCα phosphorylation of Ser890.
  • Electrophysiological studies and surface expression analysis to assess channel function.

Main Results:

  • Ser890 of the Kv11.1 ion channel is phosphorylated by PKCα.
  • PKCα-dependent phosphorylation of Ser890 influences Kv11.1 membrane density and recovery from inactivation.
  • A novel LQT2 mutation (R887H) inhibits PKCα-dependent phosphorylation of Ser890, reducing Kv11.1 surface expression and current density.

Conclusions:

  • The study provides a molecular link between a Kv11.1 mutation and LQT2 by demonstrating the role of PKCα-mediated phosphorylation of Ser890.
  • Perturbation of this phosphorylation site by mutations significantly impairs Kv11.1 channel function, contributing to LQT2 pathophysiology.

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