Developmental expression of rat cardiac troponin I mRNA

Development ◽  
1991 ◽  
Vol 112 (4) ◽  
pp. 1041-1051
Author(s):  
S. Ausoni ◽  
C. De Nardi ◽  
P. Moretti ◽  
L. Gorza ◽  
S. Schiaffino
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Mammalian Species ◽  
Calcium Sensitivity ◽  
Cardiac Troponin I ◽  
Developmental Expression ◽  
Adrenergic Stimulation ◽  
Adult Heart ◽  
Amino Terminal ◽  
The Difference

We have isolated and sequenced a full-length cDNA clone of rat cardiac troponin I (TnI). The amino acid sequence of rat cardiac TnI is highly similar to that of other mammalian species in the portion of the molecule (residues 33–210) that is also homologous to skeletal muscle TnI isoforms. In contrast, a lower degree of similarity is present in the cardiac TnI-specific amino terminal extension (residues 1–32). This region contains a conserved serine residue that has been shown to be selectively phosphorylated by cAMP-dependent protein kinase. Cardiac TnI mRNA is weakly expressed in the 18-day fetal heart and accumulates in neonatal and postnatal stages. No difference can be demonstrated between TnI mRNAs present in fetal and postnatal heart by RNAase protection assays. The fetal and neonatal, but not the adult heart, contain significant amounts of slow skeletal TnI transcripts, detected by oligonucleotide probes specific for the 5′- and 3′-untranslated regions of slow skeletal TnI mRNA. In situ hybridization studies show that cardiac and slow skeletal TnI mRNAs are coexpressed in the rat heart from embryonic day 11 throughout fetal and perinatal stages. Changes in troponin isoform expression during development may be responsible for the difference in calcium sensitivity and in the response to beta-adrenergic stimulation between fetal and adult heart.

Abstract 219: Histidine Substituted Cardiac Troponin I (a164h) Improves Survival And Protects Cardiac Contractility During Acute Hypoxia In The Aged Murine Heart.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nathan Palpant ◽  
Sharlene Day ◽  
Kimber Converso ◽  
Joseph Metzger
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Acute Hypoxia ◽  
Cardiac Contractility ◽  
Systolic Pressure ◽  
Calcium Sensitivity ◽  
The Elderly ◽  
Cardiac Troponin I ◽  
Pump Failure ◽  
Myofilament Calcium Sensitivity

Contractile dysfunction associated with ischemia is a significant cause of morbidity and mortality particularly in the elderly. Strategies designed to protect the aged heart from ischemia-mediated pump failure are needed. We have generated transgenic (Tg) mice expressing a modified form of adult cardiac troponin I, the Ca ++ -activated molecular switch of the myofilament. Consonant with the fetal isoform, this transgene encodes a histidine substitution (A164H) in the critical switch domain of TnI thus increasing myofilament calcium sensitivity in a pH-dependent manner. We hypothesized that aged mice (24 months), intrinsically susceptible to myocardial dysfunction, would retain improved cardiac contractility at baseline and during an acute hypoxic challenge by means of myofilament-mediated calcium sensitization. Methods/Results: At baseline, by echocardiography, Tg hearts had increased systolic function, with a 26% higher mean ejection fraction compared to nontransgenic (Ntg) mice: 75 ± 3% [Tg: n = 13] vs. 63 ± 4% [Ntg: n = 12], P < 0.05, with no differences in diastolic function between the groups. To study the effects of acute hypoxia on cardiac hemodynamics mice underwent microconductance Millar catheterization while ventilated with 12% oxygen. Aged Tg mice had improved survival compared to Ntg mice: time to pump failure (65% of baseline peak systolic pressure) 11.59 ± 1.25 min. [Tg: n = 3] vs. 4.11 ± 1.90 min. [Ntg: n = 3], P < 0.05. After four minutes of hypoxia, Tg mice had markedly improved cardiac contractility compared to Ntg mice with increased stroke volume (30.05 ± 4.49 uL [Tg] vs. 13.23 ± 3.21 uL [Ntg], P < 0.05), end systolic pressure (106.09 ± 11.81 mmHg [Tg] vs. 64.49 ± 4.05 mmHg [Ntg], P < 0.05) and rate of positive left ventricular pressure development (12958.66 ± 2544.68 mmHg/sec [Tg] vs. 5717.00 ± 745.67 mmHg/sec [Ntg], P = 0.05). Conclusion: An alteration in myofilament calcium sensitivity via a pH-responsive histidine button in cardiac troponin I augments baseline heart function in Tg mice over their lifetime. During acute hypoxia, cTnI A164H improves survival in aged mice by maintaining cardiac contractility, and thus holds promise for the design of gene therapeutics to treat pump failure associated with acute ischemic events in the elderly.

scholarly journals Calcium Sensitivity, Force Frequency Relation and Cardiac Troponin I: Critical Role of PKA and PKC Phosphorylation Sites

2010 ◽  
Vol 98 (3) ◽  
pp. 356a
Author(s):  
Genaro A. Ramirez-Correa ◽  
Sonia Cortassa ◽  
Brian Stanley ◽  
Wei Dong Gao ◽  
Anne M. Murphy
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Critical Role ◽  
Calcium Sensitivity ◽  
Cardiac Troponin I ◽  
Phosphorylation Sites ◽  
Force Frequency ◽  
Frequency Relation

scholarly journals The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jingsheng Liang ◽  
Katarzyna Kazmierczak ◽  
Ana I. Rojas ◽  
Yingcai Wang ◽  
Danuta Szczesna-Cordary
Keyword(s):  
Papillary Muscle ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Contractile Force ◽  
Cardiac Troponin I ◽  
Wild Type ◽  
Partial Loss ◽  
Left And Right ◽  
The Difference ◽  
State Force

We investigated the effect of the hypertrophic cardiomyopathy-linked R21C (arginine to cysteine) mutation in human cardiac troponin I (cTnI) on the contractile properties and myofilament protein phosphorylation in papillary muscle preparations from left (LV) and right (RV) ventricles of homozygous R21C+/+knock-in mice. The maximal steady-state force was significantly reduced in skinned papillary muscle strips from the LV compared to RV, with the latter displaying the level of force observed in LV or RV from wild-type (WT) mice. There were no differences in the Ca2+sensitivity between the RV and LV of R21C+/+mice; however, the Ca2+sensitivity of force was higher in RV-R21C+/+compared with RV-WT and lower in LV- R21C+/+compared with LV-WT. We also observed partial loss of Ca2+regulation at low [Ca2+]. In addition, R21C+/+-KI hearts showed no Ser23/24-cTnI phosphorylation compared to LV or RV of WT mice. However, phosphorylation of the myosin regulatory light chain (RLC) was significantly higher in the RV versus LV of R21C+/+mice and versus LV and RV of WT mice. The difference in RLC phosphorylation between the ventricles of R21C+/+mice likely contributes to observed differences in contractile force and the lower tension monitored in the LV of HCM mice.

scholarly journals Increased myofilament calcium sensitivity is associated with decreased cardiac troponin I phosphorylation in the diabetic rat heart

2021 ◽  
Author(s):  
Angela C. Greenman ◽  
Gary M. Diffee ◽  
Amelia S. Power ◽  
Gerard T. Wilkins ◽  
Olivia M. S. Gold ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Rat Heart ◽  
Troponin I ◽  
Calcium Sensitivity ◽  
Cardiac Troponin I ◽  
Diabetic Rat ◽  
Myofilament Calcium Sensitivity

Abstract 433: Regulatory and Elastic Protein Modifications in the Myocardium of Hibernating 13-lined Ground Squirrels

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Maighdlin R Patterson ◽  
Jonathan R Groening ◽  
Mark A Hiske ◽  
Hannah V Carey ◽  
Karen L Ball ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Left Ventricular ◽  
Cardiac Troponin I ◽  
Ground Squirrels ◽  
Myocardial Stiffness ◽  
Sds Page ◽  
Filling Time ◽  
The Difference

The 13-lined ground squirrel exhibits remarkable cardiac adaptation during hibernation, periods of torpor being interrupted by repeated inter-bout arousal (IBA). During IBA heart rate rises from 2-4 bpm to as great as 300 bpm. This rise in heart rate occurs over just 5 hours and remains elevated for 12-24 hours before returning to the lower heart rate. With such rapid and marked changes in heart rate, and thus filling time, myocardial stiffness and relaxation must be regulated within a short timeframe. The objective of this work was to establish post-translational modifications (PTMs) in two proteins critical to myocardial stiffness and relaxation; titin and cardiac troponin I (TnI). It was specifically hypothesized that phosphorylation during IBA would be similar to that of summer tissue and distinct from tissue isolated during torpor. Left ventricular tissue (summer, n=9; torpor, n=10; IBA, n=7) was solubilized and separated by either 2-12% gradient SDS-Page (titin) or 12.5% SDS-PAGE (TnI). Total titin phosphorylation was measured via Pro-Q Diamond Phosphoprotein/SYPRO Ruby staining. PKA-specific TnI phosphorylation was quantified via western blotting, using a primary antibody specific to Ser 23,24. While there was a tendency toward decreased total titin phosphorylation in IBA, the difference was not significant. In contrast, there were significant group effects in PKA-specific TnI phosphorylation. Phospho-TnI/Total TnI ratios were lower in torpor when compared to summer (0.22±0.12 vs. 0.68±0.,34, p<0.05). While there was no significant difference between summer and IBA (0.62±0.35), the difference between torpor and IBA failed to reach significance. This data supports the hypothesis that rapid changes in heart rates are associated with changes in cardiac troponin-I phosphorylation, a modification that contributes to rapid rates of relaxation. Further dissection of site specific titin phosphorylation will be required to assess the extent to which PTM modify titin associated stiffness. Results from this work may have significant implications in our understanding of altered compliance in human heart failure.

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