Sliding filament model

What is troponin and what is its diagnostic value?

Troponin is a three-subunit protein complex that regulates striated (skeletal and cardiac) muscle contraction (1-3). Similar to caldesmon in smooth muscle, troponin affects release from actin (3). The process of muscle contraction is best represented by the sliding filament model (3). The model illustrates heavy dependence on calcium regulation for velocity involving “loose coupling” of calcium binding to troponin to determine the rate of “cycling cross-bridges” (4-6).

Cross-bridge cycling is a two-feedback mechanism—positive and negative—depending on its activation and regulation (6). Troponin subunit Tn-T is attached to tropomyocin is attached to actin (3). When a signal transmitted to the sarcoplasmic reticulum induces release of Ca(2+) into the sarcomere, then the Ca(2+) binds to subunit Tn-C, which changes orientation of subunit Tn-I (3). The Tn-I change causes a rotation in which the structure of tropomyosin rotates actin and exposes it to myosin binding sites creating contractibility (3). This action is critical in the heart (1). It’s worth noting that any mutations of cardiac troponin would affect this process, which develops cardiomyopathies (1;7). Contraction is stopped by ATPase pumping Ca(2+) out of the sarcomere furiously (3). Once in the sarcoplastmic reticulum, the Ca(2+) is taken away by calsequestrin (3).

As a diagnostic tool for myocardial infarction, troponins are highly valued because they can detect the smallest of infarctions in comparison to other cardiac markers such as electrocardiogram, creatine kinase (CK) and CK-MB (2). Tn-T can be expressed from skeletal muscle, but Tn-I is specific to myocardium (1). Any elevation of cardiac troponins are serious markers that largely indicate a poor prognosis with unstable angina (2).

Reference List

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3. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
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5. Sata M, Yamashita H, Sugiura S, Fujita H, Momomura S, Serizawa T. A new in vitro motility assay technique to evaluate calcium sensitivity of the cardiac contractile proteins. Pflugers Arch 1995;429:443-5.
6. Landesberg A, Sideman S. Mechanical regulation of cardiac muscle by coupling calcium kinetics with cross-bridge cycling: a dynamic model. Am J Physiol 1994;267:H779-H795.
7. Lin D, Bobkova A, Homsher E, Tobacman LS. Altered cardiac troponin T in vitro function in the presence of a mutation implicated in familial hypertrophic cardiomyopathy. J Clin Invest 1996;97:2842-8.
8. Unverir P, Soner BC, Dedeoglu E, Karcioglu O, Boztok K, Tuncok Y. Renal and hepatic injury with elevated cardiac enzymes in Amanita phalloides poisoning: a case report. Hum Exp Toxicol 2007;26:757-61.
9. Livingston JC, Mabie BC, Ramanathan J. Crack cocaine, myocardial infarction, and troponin I levels at the time of cesarean delivery. Anesth Analg 2000;91:913-5, table.