TY - JOUR
T1 - Mechanisms of Disease
T2 - Ion channel remodeling in the failing ventricle
AU - Nass, Robert D.
AU - Aiba, Takeshi
AU - Tomaselli, Gordon F.
AU - Akar, Fadi G.
PY - 2008/4
Y1 - 2008/4
N2 - In an attempt to compensate for compromised hemodynamics in heart failure, neurohumoral mechanisms are activated that trigger fundamental changes in gene expression and in protein processing, trafficking and post-translational regulation, resulting in myocyte hypertrophy. Unfortunately, over time these changes become maladaptive, predisposing to myocyte loss, chamber dilatation, interstitial hyperplasia and intercellular uncoupling. Intrinsic and peripheral responses to mechanical dysfunction alter the expression and function of key ion channels and calcium-handling proteins, thereby remodeling the cellular action potential and the intracellular calcium transient. This electrophysiological remodeling renders the heart more vulnerable to ventricular arrhythmias that underlie sudden cardiac death. In this Review, we consider key ventricular ionic changes that are associated with heart failure, with the intention of identifying molecular targets for antiarrhythmic therapy.
AB - In an attempt to compensate for compromised hemodynamics in heart failure, neurohumoral mechanisms are activated that trigger fundamental changes in gene expression and in protein processing, trafficking and post-translational regulation, resulting in myocyte hypertrophy. Unfortunately, over time these changes become maladaptive, predisposing to myocyte loss, chamber dilatation, interstitial hyperplasia and intercellular uncoupling. Intrinsic and peripheral responses to mechanical dysfunction alter the expression and function of key ion channels and calcium-handling proteins, thereby remodeling the cellular action potential and the intracellular calcium transient. This electrophysiological remodeling renders the heart more vulnerable to ventricular arrhythmias that underlie sudden cardiac death. In this Review, we consider key ventricular ionic changes that are associated with heart failure, with the intention of identifying molecular targets for antiarrhythmic therapy.
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U2 - 10.1038/ncpcardio1130
DO - 10.1038/ncpcardio1130
M3 - Article
C2 - 18317475
AN - SCOPUS:41549166921
SN - 1743-4297
VL - 5
SP - 196
EP - 207
JO - Nature Clinical Practice Cardiovascular Medicine
JF - Nature Clinical Practice Cardiovascular Medicine
IS - 4
ER -