Troponin is a complex of three globular protein subunits. As a component of the muscle contractile apparatus, troponin regulates muscle contraction. It carries special significance in the diagnosis of myocardial infarction.
What is troponin?
Troponin, as a component of the actin filament, is part of the contractile unit of skeletal and cardiac muscles. It is a complex of globular proteins that, together with F-actin and tropomyosin, form the actin filament. The actin filament, in interaction with the myosin filaments, enables the muscle to contract. Because of its ability to start or stop muscle contraction, troponin, along with tropomyosin, is also known as the regulator protein of muscle. The troponin protein complex consists of three subunits, the inhibitory troponin I, troponin T responsible for tropomyosin binding, and the calcium binding troponin C.
Cardiac troponin plays an important role in the emergency diagnosis of myocardial infarction. If there is damage to the heart muscles, the subunit troponin I is released and can be detected in the blood by laboratory diagnostics. This results in a classic clinical picture that allows differentiation from other diseases of the musculature.
Anatomy and structure
Troponin is a component of actin filaments, whose interaction with myosin filaments enables muscle contraction. Both filaments form the smallest contractile unit of the muscle, the sarcomere. Troponin is a complex of globular proteins consisting of three subunits. A distinction is made between inhibitory troponin (TnI), tropomyosin-binding troponin (TnT) and calcium-binding troponin (TnC). Three troponin peptides regularly follow seven F-actin molecules in the filament. They lie as a complex almost horizontally in the actin filament. Troponin T binds on one side to tropomyosin, which is bound to F-actin, and on the other to troponin I. Troponin I has a strong affinity for F-actin, so that it is bound to it in the noncontracted state. Troponin C also binds to troponin I and is exposed to the outside. Troponin C is the smallest of the subunits and has a calcium-binding domain. Depending on the musculature, three isoforms each of troponin I and troponin T exist. Cardiac troponin (cTn) is found in cardiac muscle, and two different troponins (sTn) exist in skeletal muscle for the respective fast and slow skeletal muscle fibers.
Function and Tasks
As a component of the contractile apparatus, troponin plays a significant role in the regulation of muscle contraction. In the nonexcited state, the position of tropomyosin filaments prevents the actin filament from binding to the myosin head. Only when tropomyosin is pulled further inside the filament helix by troponin T is the binding site for myosin exposed. This change in position is achieved by a conformational change in the troponin complex as a result of an increase in calcium concentration. Calcium is released into the muscle fibers by electrical excitation of the plasma membrane. Troponin C is the calcium receptor in the actin filament because it has a calcium-binding domain. This in turn consists of two structures, each carrying four calcium binding sites. Two of these binding sites each have high affinity for calcium, and two have low affinity. Only the low-affinity binding sites are involved in contraction. The conformational change of troponin C after calcium binding is directly transmitted by troponin T to tropomyosin, which is pulled further into the groove between the actin strands and releases the binding site for the myosin head. At the same time, the inhibitory effect of troponin I on the ATPase is abolished and ATP can be cleaved at the myosin, resulting in the kinking of the myosin head. The actin filament is pulled along the myosin filament and the muscle contracts. The binding of myosin and actin is disrupted by the attachment of new ATP to the myosin. The calcium level in the muscle fiber decreases and the tropomyosin filaments again cover the myosin binding site. The muscle is in relaxation.
Diseases
The troponin value represents the most important laboratory diagnostic parameter for myocardial infarction. Cardiac troponin, particularly troponin T and troponin I, is released into the blood when the myocardium is damaged.The troponin level can be determined in serum, plasma or whole blood. The concentration of troponin in the blood shows a typical course after a heart attack, so that it can be distinguished from other myocardial damage. An increase in troponin occurs approximately 3-8 hours after the onset of myocardial infarction. The highest values can be measured 12-96 hours after onset. It takes about two weeks for the troponin level in the blood to return to normal after a heart attack. If the troponin level shows a decreasing course, it is most likely not a heart attack but another cause such as overstretching, inflammation of the skeletal muscles or other injuries. Elevated troponin levels are also found in a variety of other conditions that involve destruction of muscle tissue. For example, troponin levels increase in cases of dysfunction or inflammation of the heart, diseases of the blood vessels, inflammation or injury of the skeletal muscles, stroke, dysfunction of the lungs, or burns and sepsis, among others. Troponin elevation is considered a major risk factor for mortality after surgery. Since there are several days between a troponin rise and the patient’s death, timely intervention with medication is possible. The increase in troponin levels after heavy physical exertion, such as endurance sports, has no clinical significance. In most cases, levels normalize within a few hours, returning to normal after a maximum of 72 hours.
