Gomes Aldrin V, Venkatraman Gayathri, Potter James D
Dept. of Molecular and Cellular Pharmacology, Leonard M. Miller School of Medicine at the University of Miami, 1600 N.W. 10th Avenue, Miami, FL 33136, USA.
Ann N Y Acad Sci. 2005 Jun;1047:30-7. doi: 10.1196/annals.1341.003.
Troponin (Tn) is made up of three subunits, troponin T (TnT), troponin I (TnI), and troponin C (TnC). In cardiac muscle, TnI can exist as two isoforms, slow skeletal TnI (ssTnI) or cardiac TnI (cTnI), whereas TnT occurs as multiple isoforms. The predominant form of TnI in fetal cardiac muscle is ssTnI, which is derived from a different gene than cTnI. However, the predominant form of cardiac TnT (cTnT) in fetal muscle is cTnT1, which is derived from the same gene that produces the adult cTnT isoform (cTnT3). Fetal cardiac muscle is more sensitive to Ca(2+) than adult muscle and this may be due in part to the fetal cTnT1 and ssTnI isoforms. cTnT1 and/or ssTnI by themselves cause a significant increase in Ca(2+) sensitivity when compared to cTnT3 and/or cTnI. Mutations in the gene for cTnT can cause hypertrophic cardiomyopathy or dilated cardiomyopathy (DCM). Investigation of DCM mutations in the fetal cTnT1 isoform showed that the cTnT isoform is an important determinant of the effect of the mutation. The TnI isoform also affects the physiological function of the cardiac muscle. The presence of both the fetal TnT isoform, containing a DCM mutation, and ssTnI results in larger changes in Ca(2+) sensitivity than the same DCM mutant in the adult TnT isoform and in the presence of cTnI (when compared to their respective wild-type TnT controls). These recent results suggest that some mutations may have different severities in fetal and adult hearts.
肌钙蛋白（Tn）由三个亚基组成，即肌钙蛋白T（TnT）、肌钙蛋白I（TnI）和肌钙蛋白C（TnC）。在心肌中，TnI可以以两种异构体形式存在，即慢骨骼肌TnI（ssTnI）或心肌TnI（cTnI），而TnT则以多种异构体形式存在。胎儿心肌中TnI的主要形式是ssTnI，它与cTnI来自不同的基因。然而，胎儿肌肉中心肌TnT（cTnT）的主要形式是cTnT1，它与产生成人cTnT异构体（cTnT3）的基因相同。胎儿心肌比成人肌肉对Ca(2+)更敏感，这可能部分归因于胎儿cTnT1和ssTnI异构体。与cTnT3和/或cTnI相比，cTnT1和/或ssTnI自身会导致Ca(2+)敏感性显著增加。cTnT基因的突变可导致肥厚型心肌病或扩张型心肌病（DCM）。对胎儿cTnT1异构体中DCM突变的研究表明，cTnT异构体是突变效应的重要决定因素。TnI异构体也会影响心肌的生理功能。与成人TnT异构体中相同的DCM突变体以及存在cTnI时（与各自的野生型TnT对照相比），同时存在含有DCM突变的胎儿TnT异构体和ssTnI会导致Ca(2+)敏感性发生更大的变化。这些最新结果表明，某些突变在胎儿和成人心脏中的严重程度可能不同。
