Troponin phosphorylation and myofilament Ca2+ -sensitivity in heart failure: Increased or decreased?

Heart failure is characterised by depressed myocyte contractility and is considered to involve a complex malfunction of adrenergic regulation, Ca2+-handling and the contractile apparatus. Most studies on the contractile apparatus have focussed on troponin, the Ca2+-dependent regulator of myofibrillar activity. Importantly, phosphorylation of troponin I secondary to beta-adrenergic receptor activation is known to induce reduced myofilament Ca(2+)sensitivity. In muscle samples from explanted failing human hearts, troponin I phosphorylation levels are very low and Ca2+-sensitivity is high. In contrast, some animal models used to study the mechanisms of heart failure give the opposite result-high levels of troponin I phosphorylation and low Ca2+-sensitivity. Which is right? (C) 2008 Elsevier Inc. All rights reserved.