Journal article
Electrical remodeling of cardiac myocytes from mice with heart failure due to the overexpression of tumor necrosis factor-α
American journal of physiology. Heart and circulatory physiology, Vol.290(5), pp.H2098-2107
05/2006
DOI: 10.1152/ajpheart.00097.2005
PMID: 16339842
Abstract
Mice that overexpress the inflammatory cytokine tumor necrosis factor-alpha in the heart (TNF mice) develop heart failure characterized by atrial and ventricular dilatation, decreased ejection fraction, atrial and ventricular arrhythmias, and increased mortality (males > females). Abnormalities in Ca2+ handling, prolonged action potential duration (APD), calcium alternans, and reentrant atrial and ventricular arrhythmias were previously observed with the use of optical mapping of perfused hearts from TNF mice. We therefore tested whether altered voltage-gated outward K+ and/or inward Ca2+ currents contribute to the altered action potential characteristics and the increased vulnerability to arrhythmias. Whole cell voltage-clamp recordings of K+ currents from left ventricular myocytes of TNF mice revealed an approximately 50% decrease in the rapidly activating, rapidly inactivating transient outward K+ current Ito and in the rapidly activating, slowly inactivating delayed rectifier current IK,slow1, an approximately 25% decrease in the rapidly activating, slowly inactivating delayed rectifier current IK,slow2, and no significant change in the steady-state current Iss compared with controls. Peak amplitudes and inactivation kinetics of the L-type Ca2+ current ICa,L were not altered. Western blot analyses revealed a reduction in the proteins underlying Kv4.2, Kv4.3, and Kv1.5. Thus decreased K+ channel expression is largely responsible for the prolonged APD in the TNF mice and may, along with abnormalities in Ca2+ handling, contribute to arrhythmias.
Details
- Title: Subtitle
- Electrical remodeling of cardiac myocytes from mice with heart failure due to the overexpression of tumor necrosis factor-α
- Creators
- Polina S Petkova-Kirova - Department of Cell Biology and Physiology,University of Pittsburgh, Pittsburgh, PA 15261, USAErdal GursoyHaider MehdiCharles F McTiernanBarry LondonGuy Salama
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.290(5), pp.H2098-2107
- Publisher
- United States
- DOI
- 10.1152/ajpheart.00097.2005
- PMID
- 16339842
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Grant note
- HL-057929 / NHLBI NIH HHS HL-59614 / NHLBI NIH HHS HL-66096 / NHLBI NIH HHS HL-70722 / NHLBI NIH HHS
- Language
- English
- Date published
- 05/2006
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984025569902771
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