Posttranslational Modifications of Troponin in Cardiac Adaptation and Failure

DOI: 10.5176/2382-607X_ARP14.13

Authors: J.-P. Jin, MD, PhD

Abstract: Troponin plays a central role in regulating the contraction and relaxation of vertebrate striated muscles. Cardiac troponin consists of three protein subunits: The Ca2+ receptor troponin C (TnC), the actomyosin ATPase inhibitory subunit troponin I (TnI), and the tropomyosin-binding, thin filament anchoring subunit troponin T (TnT). Cardiac TnI and cardiac TnT both undergo posttranslational modifications that play important roles in the regulation of cardiac muscle contractility and adaptations in stress conditions and heart failure. Phosphorylation and proteolysis modifications of cardiac TnI and cardiac TnT result in potent effects on the structure-function of troponin. N-terminal phosphorylation of cardiac TnI by PKA or a restrictive N-terminal truncation of cardiac TnI in adaptation to heart failure selectively increases the relaxation of cardiac muscle and enhances diastolic function of the heart. This function significantly extends the range of the Frank-Starling responses of the ventricular muscle to increase cardiac output at increased preload. In contrast, a restrictive N-terminal truncation of cardiac TnT, which selectively removes the hypervariable region, selectively and moderately reduces the contractile velocity of cardiac muscle and prolongs the rapid ejection phase of left ventricle against high afterload. It is very interesting to observe that modifications of the two subunits of troponin selectively regulate the diastolic and systolic functions of the heart. The physiological and pathophysiological significances are discussed for impacts on cardiac muscle contractility, heart function, and adaptation in health and diseases.

Keywords: Heart, cardiac muscle, failure, contractility, troponin, cardiac physiology and cell biology