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 Ca2+ 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?
Marston
Steven B
SB
Cardiovascular Science, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW36LY, UK. s.marston@imperial.ac.uk
de Tombe
Pieter P
PP
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D001671:Biochemistry / Q000379:methods; D002118:Calcium / Q000378:metabolism; D002309:Cardiology / Q000379:methods; D004195:Disease Models, Animal; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D009119:Muscle Contraction; D009132:Muscles / Q000378:metabolism; D010766:Phosphorylation; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D014336:Troponin / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D014336:Troponin; D002118:Calcium