Long QT and ventricular arrhythmias in transgenic mice expressing the N terminus and first transmembrane segment of a voltage-gated potassium channel

Barry London; Andreas Jeron; Jun Zhou; Peter Buckett; Xingiang Han; Gary F Mitchell; Gideon Koren

doi:10.1073/pnas.95.6.2926

Back

Long QT and ventricular arrhythmias in transgenic mice expressing the N terminus and first transmembrane segment of a voltage-gated potassium channel

Journal article

Open access

Peer reviewed

Long QT and ventricular arrhythmias in transgenic mice expressing the N terminus and first transmembrane segment of a voltage-gated potassium channel

Barry London, Andreas Jeron, Jun Zhou, Peter Buckett, Xingiang Han, Gary F Mitchell and Gideon Koren

Proceedings of the National Academy of Sciences - PNAS, Vol.95(6), pp.2926-2931

03/17/1998

DOI: 10.1073/pnas.95.6.2926

PMCID: PMC19671

PMID: 9501192

Files and links (1)

url

https://doi.org/10.1073/pnas.95.6.2926View

Published (Version of record) Open Access

Abstract

Voltage-gated potassium channels control cardiac repolarization, and mutations of K+ channel genes recently have been shown to cause arrhythmias and sudden death in families with the congenital long QT syndrome. The precise mechanism by which the mutations lead to QT prolongation and arrhythmias is uncertain, however. We have shown previously that an N-terminal fragment including the first transmembrane segment of the rat delayed rectifier K+ channel Kv1.1 (Kv1.1N206Tag) coassembles with other K+ channels of the Kv1 subfamily in vitro, inhibits the currents encoded by Kv1.5 in a dominant-negative manner when coexpressed in Xenopus oocytes, and traps Kv1.5 polypeptide in the endoplasmic reticulum of GH3 cells. Here we report that transgenic mice overexpressing Kv1.1N206Tag in the heart have a prolonged QT interval and ventricular tachycardia. Cardiac myocytes from these mice have action potential prolongation caused by a significant reduction in the density of a rapidly activating, slowly inactivating, 4-aminopyridine sensitive outward K+ current. These changes correlate with a marked decrease in the level of Kv1.5 polypeptide. Thus, overexpression of a truncated K+ channel in the heart alters native K+ channel expression and has profound effects on cardiac excitability.

Biological Sciences

Details

Title: Subtitle: Long QT and ventricular arrhythmias in transgenic mice expressing the N terminus and first transmembrane segment of a voltage-gated potassium channel
Creators: Barry London - Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; and
Andreas Jeron - Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; and
Jun Zhou - Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; and
Peter Buckett - Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; and
Xingiang Han - Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; and
Gary F Mitchell - Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; and
Gideon Koren - Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; and
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.95(6), pp.2926-2931
DOI: 10.1073/pnas.95.6.2926
PMID: 9501192
PMCID: PMC19671
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 03/17/1998
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984025329302771

Metrics

27 Record Views

141 Times Cited - Web of Science

See more details