Troponin complex

Troponin complex is a heteromeric protein playing an important role in the regulation of skeletal and cardiac muscle contraction. Troponin complex consists of three different subunits – troponin T (TnT), troponin I (TnI) and troponin C (TnC). Each subunit is responsible for a part of troponin complex function. TnT is a tropomyosin-binding subunit which regulates the interaction of troponin complex with thin filaments; TnI inhibits ATP-ase activity of acto-myosin; TnC is a Ca2+ - binding subunit, playing the main role in Ca2+ dependent regulation of muscle contraction. TnT and TnI in cardiac muscle are presented by forms different from those in skeletal muscles. Two isoforms of TnI and two isoforms of TnT are expressed in human skeletal muscle tissue (skTnI and skTnT). Only one tissue-specific isoform of TnI is described for cardiac muscle tissue (cTnI), whereas the existence of several cardiac specific isoforms of TnT (cTnT) are described in the literature. No cardiac specific isoforms are known for human TnC. TnC in human cardiac muscle tissue is presented by an isoform typical for slow skeletal muscle. Another form of TnC, fast skeletal TnC isoform, is more typical for fast skeletal muscles. cTnI is expressed only in myocardium. No examples of cTnI expression in healthy or injured skeletal muscle or in other tissue types are known. cTnT is probably less cardiac specific. Expression of cTnT in skeletal tissue of patients with chronic skeletal muscle injuries has been described. First cTnI. and later cTnT were used as markers of cardiac cell death. Now both proteins are widely used for the diagnosis of acute myocardial infarction (AMI), unstable angina, post-surgery myocardium trauma and some other diseases related with cardiac muscle injury. Both markers can be detected in patient’s blood 3–6 hours after onset of the chest pain, reaching peak level within 16–30 hours. Elevated concentration of cTnI and cTnT in blood samples can be detected even 5–8 days after onset of the symptoms, making both proteins useful also for the late diagnosis of AMI.

Inside the cardiac troponin complex the strongest interaction between molecules has been demonstrated for cTnI – TnC binary complex especially in the presence of Ca2+ ( KA = 1.5x10−8 M−1). TnC, forming a complex with cTnI, changes the conformation of cTnI molecule and shields part of it’s surface. According to the latest data cTnI is released in the blood stream of the patient in the form of binary complex with TnC or ternary complex with cTnT and TnC. cTnI-TnC complex formation plays an important positive role in improving the stability of cTnI molecule. cTnI, which is extremely unstable in its free form, demonstrates significantly better stability in complex with TnC or in ternary cTnI-cTnT-TnC complex. It has been demonstrated that stability of cTnI in native complex is significantly better than stability of the purified form of the protein or the stability of cTnI in artificial troponin complexes combined from purified proteins.

HyTest’s Troponin I-T-C Complex has been chosen by AACC cTnI Standardization Subcommittee for international reference material. The standard reference material (SRM 2921) is available from National Institute of Standards and Technology. Additional information can be found from www.nist.gov.