Journal article
Long QT and ventricular arrhythmias in transgenic mice expressing the N terminus and first transmembrane segment of a voltage-gated potassium channel
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
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.
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; andAndreas Jeron - Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; andJun Zhou - Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; andPeter Buckett - Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; andXingiang Han - Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; andGary F Mitchell - Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; andGideon 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
- Publisher
- The National Academy of Sciences
- DOI
- 10.1073/pnas.95.6.2926
- PMID
- 9501192
- PMCID
- PMC19671
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Language
- English
- Date published
- 03/17/1998
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984025329302771
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