Mechanisms of disease: ion channel remodeling in the failing ventricle.
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.
Nass
Robert D
RD
Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
Aiba
Takeshi
T
Tomaselli
Gordon F
GF
Akar
Fadi G
FG
D000200:Action Potentials / Q000502:physiology; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism* / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology*
D007473:Ion Channels