The Role of Troponins in Muscle Contraction

Gomes, Aldrin V.; Potter, James D.; Szczesna‐Cordary, Danuta

doi:10.1080/15216540216037

Cited by 168 publications

(137 citation statements)

References 84 publications

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“…7 Troponin T is the largest subunit in the troponin complex, which attaches to tropomyosin and actin to facilitate cross-linking with the myosin thick filament leading to contraction during excitation. 8 Serum cardiac troponin T (cTnT) is a marker of cardiac injury and mortality in adults and is a good marker of myocardial injury in perinatally asphyxiated neonates. 9 cTnT levels are higher in premature infants with respiratory distress syndrome (RDS).…”

Section: Introductionmentioning

confidence: 99%

Cardiac troponin T and N-terminal-pro-B type natriuretic peptide reflect myocardial function in preterm infants

et al. 2008

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Background: Cardiovascular compromise is increasingly recognized in preterm infants. Currently, echocardiography is the best tool to assess myocardial contractility and guide management. Elevated levels of cardiac troponin T (cTnT) and N-terminal-pro-B type natriuretic peptide (NTpBNP) are associated with poor myocardial contractility and low cardiac output in adults.Objective: To examine the range of cTnT and NTpBNP in preterm infants, to correlate NTpBNP and cTnT with echocardiographic markers of cardiac function and to assess the influence of antenatal and postnatal factors on these biochemical markers.Study Design: Plasma concentrations of cTnT and NTpBNP were measured in infants <1500 g at 12 h of age. These were correlated with simultaneous echocardiographic measures of myocardial function and output. Antenatal data, infant demographics and postnatal characteristics were prospectively recorded.Result: A total of 80 infant had samples taken and echocardiography performed. Their median (interquartile range) cTnT and NTpBNP values were 0.20 mg l À1 (0.11 to 0.40) and 1273 pmol l À1 (664 to 2798), respectively. There was a significant inverse correlation between cTnT and echocardiographic markers of myocardial function and stroke volume. NTpBNP significantly correlated with left atrial to aortic root ratio (LA:Ao). There was a weaker but significant negative correlation between NTpBNP and left ventricular (LV) function. The assays were not influenced by gestation, birth weight, gender or mode of delivery.Conclusion: cTnT and NTpBNP are correlated with echocardiographic measures of cardiac performance in preterm infants. Measurement of levels in the first hours of life may provide useful information regarding myocardial function and volume loading.

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Section: Introductionmentioning

confidence: 99%

Cardiac troponin T and N-terminal-pro-B type natriuretic peptide reflect myocardial function in preterm infants

et al. 2008

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“…2 plays many important roles in striated muscle contraction, providing structural stability to the troponin complex and actively participating in the Ca 2ϩ -dependent regulation of contraction (1)(2)(3)(4)(5). TnT was first associated with heart disease in 1994 where three mutations were reported to cause Familial Hypertrophic Cardiomyopathy (FHC) (6).…”

Section: Troponin T (Tnt)mentioning

confidence: 99%

F110I and R278C Troponin T Mutations That Cause Familial Hypertrophic Cardiomyopathy Affect Muscle Contraction in Transgenic Mice and Reconstituted Human Cardiac Fibers

Hernandez

Szczesna‐Cordary

Knollmann

et al. 2005

Journal of Biological Chemistry

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We have studied the physiological effects of the troponin T (TnT) F110I and R278C mutations associated with familial hypertrophic cardiomyopathy (FHC) in humans. Three to four-month-old transgenic (Tg) mice expressing F110I-TnT and R278C-TnT did not develop significant hypertrophy or ventricular fibrosis even after chronic exercise challenge. The F110I mutation impaired acute exercise tolerance, whereas R278C did not. Skinned papillary muscle fibers from transgenic mice expressing F110I-TnT demonstrated increased Ca 2؉ sensitivity of force and ATPase activity, and likewise an increased Ca 2؉ sensitivity of force was observed in F110I-TnT-reconstituted human cardiac muscle preparations. In contrast, no changes in force or the ATPase-pCa dependencies were observed in transgenic R278C fibers or in human fibers reconstituted with the R278C-TnT mutant. The maximal level of force development was dramatically decreased in both transgenic mice. However, the maximal ATPase was not different (R278C-TnT) or only slightly less (F110I-TnT) than that of non-Tg and WT-Tg littermates. Consequently, their ratios of ATPase/force (energy cost) at all Ca 2؉ concentrations were dramatically higher compared with non-Tg and WT-Tg fibers. This increase in energy cost most likely results from a decrease in force per myosin cross-bridge, because forcing all cross-bridges into the force generating state by substitution of MgADP for MgATP in maximum contracting solutions resulted in the same increase in maximal force (15%) in all transgenic and non-transgenic preparations. The combination of increased Ca 2؉ sensitivity and energy cost in the F110I hearts may be responsible for the greater severity of this phenotype compared with the R278C mutation.

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“…The traces have been normalized and displaced vertically for clarity. C also shows the time course of the increase in Quin-2 fluorescence as Ca 2ϩ was removed by Quin-2 from the N-terminal site of cTnC F27W 2 , and 1 mM DTT, pH 7.0, was rapidly mixed with an equal volume of EGTA (10 mM) in the same buffer. Trp fluorescence was monitored through a UV-transmitting black glass filter (UG1 from Oriel, Stratford, CT) with excitation at 285 nm.…”

Section: Using Acts To Estimate the Ca 2ϩ Association Rates To The N-mentioning

confidence: 99%

Designing Calcium-sensitizing Mutations in the Regulatory Domain of Cardiac Troponin C

Tikunova

Davis

2004

Journal of Biological Chemistry

150

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As anticipated, these selected hydrophobic residue substitutions increased the calcium affinity of the regulatory domain of cardiac troponin C F27W ϳ2.1-15.2-fold. Surprisingly, the increased calcium affinity caused by the hydrophobic residue substitutions was largely due to faster calcium association rates (2.6 -8.7-fold faster) rather than to slower calcium dissociation rates (1.2-2.9-fold slower). The regulatory N-domains of cardiac troponin C F27W and its mutants were also able to bind magnesium competitively and with physiologically relevant affinities (1.2-2.7 mM). The design of calcium-sensitizing cardiac troponin C mutants presented in this work enhances the understanding of how to control cation binding properties of EF-hand proteins and ultimately their structure and physiological function.

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The Role of Troponins in Muscle Contraction

Cited by 168 publications

References 84 publications

Cardiac troponin T and N-terminal-pro-B type natriuretic peptide reflect myocardial function in preterm infants

Cardiac troponin T and N-terminal-pro-B type natriuretic peptide reflect myocardial function in preterm infants

F110I and R278C Troponin T Mutations That Cause Familial Hypertrophic Cardiomyopathy Affect Muscle Contraction in Transgenic Mice and Reconstituted Human Cardiac Fibers

Designing Calcium-sensitizing Mutations in the Regulatory Domain of Cardiac Troponin C

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