Troponin

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Troponin is a protein complex that confers calcium sensitivity to muscle cells. Calcium fluctuations are pivotal to each muscle contraction.

Troponin is found in both skeletal muscle and cardiac muscle, but the specific versions of troponin differ between types of muscle, due to the expression of different genes (in the heart, for example).

Discussions of troponin often pertain to its functional characteristics and/or to its usefulness as a diagnostic marker for various heart disorders.

Contents 1 Functional characteristics 1.1 Role of troponins 1.2 Subtypes 2 Diagnostic use 3 Sources

[edit] Functional characteristics

[edit] Role of troponins

Both cardiac and skeletal muscles are exquisitely controlled by changes in the intracellular calcium concentration. When calcium rises, the muscles contract, and when calcium falls the muscles relax.

Troponin is a component of thin filaments (along with actin and tropomyosin), and is the protein to which calcium binds to accomplish this regulation. Troponin has three subunits, TnC, TnI, and TnT. When calcium is bound to specific sites on TnC, the structure of the thin filament changes in such a manner that myosin (a molecular motor organized in muscle thick filaments) attaches to thin filaments and produces force and/or movement. In the absence of calcium, tropomyosin interferes with this action of myosin, and therefore muscles remain relaxed.

Individual subunits serve different functions:

• Troponin C binds to calcium ions to produce movement
• Troponin T binds to tropomyosin, interlocking them to form a troponin-tropomyosin complex
• Troponin I binds to actin in thin myofilaments to hold the troponin-tropomyosin complex in place

[edit] Subtypes

Of the troponin units C, I and T there are various tissue-specific subtypes:

• Troponin C:
  • Slow troponin C, TNNC1 (3p21.3-p14.3, Mendelian Inheritance in Man (OMIM) 191040)
  • Fast troponin C, TNNC2 (20q12-q13.11, 2191039
• Troponin I:
  • Slow-twitch skeletal muscle isoform troponin I, TNNI1 (1q31.3, 191042)
  • Fast-twitch skeletal muscle isoform troponin I, TNNI2 (11p15.5, 191043)
  • Cardiac troponin I, TNNI3 (19q13.4, 191044)
• Troponin T:
  • Slow skeletal troponin T1, TNNT1 (19q13.4, 191041)
  • Cardiac troponin T2, TNNT2 (1q32, 191045)
  • Fast skeletal troponin T3, TNNT3 (11p15.5, 600692)

[edit] Diagnostic use

Certain subtypes of troponin (cardiac troponin I and T) are very sensitive and specific indicators of damage to the heart muscle (myocardium). They are measured in the blood to differentiate between unstable angina and myocardial infarction (heart attack) in patients with chest pain. A patient who had suffered from a myocardial infarction would have an area of damaged heart muscle and so would have elevated cardiac troponin levels in the blood.^[1]

It is important to note that cardiac troponins are a marker of all heart muscle damage, not just myocardial infarction. Other conditions that directly or indirectly lead to heart muscle damage can also therefore increase troponin levels:^[2]

• Cardiac:
  • Cardiac amyloidosis
  • Cardiac contusion
  • Cardiac surgery and heart transplant
  • Defibrillation
  • Closure of atrial septal defects
  • Coronary vasospasm
  • Dilated cardiomyopathy
  • Heart failure
  • Hypertrophic cardiomyopathy
  • Myocarditis
  • Percutaneous coronary intervention
  • Radiofrequency ablation
  • Supraventricular tachycardia
• Non-cardiac:
  • Critical illness, e.g. sepsis
  • High-dose chemotherapy
  • Primary pulmonary hypertension
  • Pulmonary embolism
  • Renal failure
  • Subarachnoid hemorrhage
  • Scorpion venom
  • Stroke
  • Very heavy exercise (marathon)

Cardiac troponin T and I are measured by immunoassay methods. A single manufacturer distributes cTnT but a host of diagnostic companies make cTnI methods available on many different immunoassay platforms.^[3]

Drug-induced cardiotoxicity is common to all classes of therapeutic drugs. It is essential that cardiotoxicity is detected with a high degree of sensitivity and specificity. The newly developed troponins are especially useful in this context^[4]

[edit] Sources

1. ^ Antman EM, Tanasijevic MJ, Thompson B, Schactman M, McCabe CH, Cannon CP, Fischer GA, Fung AY, Thompson C, Wybenga D, Braunwald E. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996;335:1342-9. PMID 8857017.
2. ^ Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ 2004;328:1028-9. PMID 15117768.
3. ^ Collinson PO, Boa FG, Gaze DC. Measurement of cardiac troponin. Ann Clin Biochem 2001;38:423-449. PMID 11587122.
4. ^ Gaze DC, Collinson PO. Cardiac troponins as biomarkers of drug- and toxin-induced cardiac toxicity and cardioprotection. Expert Opin Drug Metab Toxicol 2005;1:715-725. PMID 16863435.

Muscle tissue  v • d • e

skeletal muscle/general: epimysium, fascicle, perimysium, endomysium, muscle fiber, myofibril sarcomere (a, i, and h bands; z and m lines), myofilaments (thin filament/actin, thick filament/myosin, elastic filament/titin), tropomyosin, troponin neuromuscular junction, intrafusal muscle fibers, extrafusal muscle fiber, motor unit, muscle spindle, sliding filament mechanism myoblast, satellite cells, sarcoplasm, sarcolemma, sarcoplasmic reticulum, T-tubule cardiac muscle: myocardium, intercalated disc smooth muscle: calmodulin, vascular smooth muscle