The Cardiac Troponin C Isoform and the Length Dependence of Ca2+Sensitivity of Tension in Myocardium

Akella, Arvind B.; Hong, Seonki; Sonnenblick, Edmund H.; Rao, Venu G.; Gulati, Jagdish

doi:10.1006/jmcc.1996.0282

Cited by 15 publications

(9 citation statements)

References 5 publications

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“…Other proposed mechanisms include endogenous catecholamines release, increased availability of intra-cellular calcium to bind to contractile proteins (Vahl et al 1998), changes in the af®nity for intra-cellular calcium by contractile proteins, predominantly troponin C (Akella et al 1997) and, alterations in the af®nity and density of cardiac b-adrenoreceptors and changes in the coronary¯ow and perfusion under conditions of increased pressure load. The greater stroke volume seen after banding in our current study does not support a shorter deactivation time (secondary to reduced stroke volume) as an explanation for the RV contractility.…”

Section: Homeometric Autoregulationmentioning

confidence: 99%

“…The greater stroke volume seen after banding in our current study does not support a shorter deactivation time (secondary to reduced stroke volume) as an explanation for the RV contractility. Other proposed mechanisms include endogenous catecholamines release, increased availability of intra-cellular calcium to bind to contractile proteins (Vahl et al 1998), changes in the af®nity for intra-cellular calcium by contractile proteins, predominantly troponin C (Akella et al 1997) and, alterations in the af®nity and density of cardiac b-adrenoreceptors and changes in the coronary¯ow and perfusion under conditions of increased pressure load.…”

Section: Homeometric Autoregulationmentioning

confidence: 99%

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Acute effects of pulmonary artery banding in sheep on right ventricle pressure–volume relations: relevance to the arterial switch operation

Hon

Steendijk

Khan

et al. 2001

Acta Physiologica Scandinavica

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The first stage of the two-stage arterial switch operation (ASO) for transposition of the great arteries (TGA) is associated with depressed ventricular function and an unstable immediate post-operative course. It is unclear if this is because of the acute increase in afterload of the thin-walled, low-pressure ventricle by pulmonary artery banding (PAB). To determine the acute effects of afterload increase on the contractile function of thin-walled ventricles, we studied the right ventricular pressure-volume relations of seven sheep before and 30 min after PAB using combined pressure-conductance catheters during inflow reduction. Load independent indices of systolic and diastolic performance were derived from these relations. Pulmonary artery banding increased the mean ratio between right and left ventricular systolic pressure from 0.34 +/- 0.05 to 0.64 +/- 0.10, P < 0.05 (mean +/- SD). There were no significant changes in heart rate and end-systolic volume after banding although there was an incremental trend in the end-diastolic volume and stroke volume. Right ventricular output (530 +/- 163-713 +/- 295 mL min (-1), P < 0.05), slope of the end-systolic pressure-volume relation (ESPVR) (3.7 +/- 2.8-10.0 +/- 4.8 mmHg mL (-1), P < 0.05) and slope of the pre-load recruitable stroke work (PRSW) relation (9.6 +/- 1.8-15.0 +/- 3.1 mmHg, P < 0.05) were significantly increased indicating improved contractile state after banding. The diastolic function curve was unchanged after banding although the right ventricle (RV) was operating at a larger end-diastolic volume. Hence, the RV of sheep responded to acute pressure overload by demonstrating enhanced contractility and evidence of the Frank-Starling mechanism without associated change in right ventricular diastolic performance.

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Section: Homeometric Autoregulationmentioning

confidence: 99%

Section: Homeometric Autoregulationmentioning

confidence: 99%

Acute effects of pulmonary artery banding in sheep on right ventricle pressure–volume relations: relevance to the arterial switch operation

Hon

Steendijk

Khan

et al. 2001

Acta Physiologica Scandinavica

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“…Results from a number of studies have shown that the Ca 2ϩ sensitivity of tension 11,23 and Ca 2ϩ -binding affinity of troponin C 10 in osmotically compressed preparations at short SLs were similar to values seen under control conditions at long SLs. Alternatively, length-dependent modulation of myocardial contraction has been proposed to be due to cardiac troponin C, which acts as a unique "length sensor" in myocardium, 24,25 although this hypothesis has received little experimental support from other investigators. For example, slow-twitch soleus muscle does not exhibit SL dependence of Ca 2ϩ binding, 12 despite the fact that the troponin C isoform in cardiac and soleus muscles is identical.…”

Section: Nem-s1 Nearly Eliminates Sl Dependence Of Myofilament Ca 2؉ mentioning

confidence: 99%

Strong Binding of Myosin Modulates Length-Dependent Ca ²⁺ Activation of Rat Ventricular Myocytes

Fitzsimons

Moss

1998

Circulation Research

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Abstract-Reductions in sarcomere length (SL) and concomitant increases in interfilament lattice spacing have been shown to decrease the Ca 2ϩ sensitivity of tension in myocardium. We tested the idea that increased lattice spacing influences the SL dependence of isometric tension by reducing the probability of strong interactions of myosin crossbridges with actin, thereby decreasing cooperative activation of the thin filament. Single ventricular myocytes were isolated by enzymatic digestion of rat hearts and were subsequently rapidly skinned. Maximal tension and Ca 2ϩ sensitivity of tension (ie, pCa 50 ) were measured in the absence and presence of N-ethylmaleimide-modified myosin subfragment 1 (NEM-S1) at both short and long SLs. NEM-S1, a strong-binding non-tension-generating derivative of the myosin head, was applied to single skinned myocytes to cooperatively promote strong binding of endogenous myosin crossbridges. Compared with control myocytes at SL of Ϸ1.90 m, application of NEM-S1 markedly increased submaximal Ca 2ϩ -activated tensions and thereby increased Ca 2ϩ sensitivity; ie, pCa 50 increased from 5.40Ϯ0.02 to 5.52Ϯ0.02 pCa units in the presence of NEM-S1. Furthermore, NEM-S1 treatment reversibly eliminated the SL dependence of the Ca 2ϩ sensitivity of tension, in that the ⌬pCa 50 between short and long lengths was 0.02Ϯ0.01 pCa units in the presence of NEM-S1 compared with a ⌬pCa 50 of 0.10Ϯ0.01 pCa units in control myocytes. From these results we conclude that the decrease in the Ca 2ϩ sensitivity of tension at short SL results predominantly from decreased cooperative activation of the thin filament due to reductions in the number of strong-binding crossbridges. (Circ Res. 1998;83:602-607.) Key Words: Ca 2ϩ sensitivity Ⅲ muscle length Ⅲ ventricular myocyte W ithin normal physiological limits, alterations in ventricular end-diastolic volume result in marked changes in cardiac output. Since the heart normally operates on the positive slope of the pressure-volume relationship, increases in end-diastolic volume induce the heart to increase either stroke volume, ejection pressure, or both in a way that closely matches myocardial work to the load on the heart. This intrinsic ability of the heart to alter ventricular peak systolic pressure due to beat-to-beat variations in end-diastolic volume constitutes the basis for the well-known Frank-Starling relationship. The present study was performed to investigate molecular mechanisms underlying this relationship.Twitch tension and Ca 2ϩ sensitivity of tension (ie, pCa 50 ) in cardiac muscle preparations are known to decrease as sarcomere length (SL) is shortened within its working range (ie, from Ϸ2.30 m to Ϸ1.80 m).1,2 The regulation of myocardial contraction requires the binding of Ca 2ϩ to a low-affinity site on troponin C, which permits strong interactions of myosin crossbridges with actin.3 However, experimental evidence has shown that Ca 2ϩ alone is unable to fully activate the thin filament: complete activation, in terms of force and the kinetics of for...

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“…TnC is known to exist only as two isoforms, one fast (TnC-f) and one slow/cardiac (TnC-s/cTnC), which differ on the basis of the number of active Ca 2+ -binding sites [7] and the degree to which Ca 2+ -binding increases the affinity of TnC for troponin I (TnI) [8]. These differences have been shown to affect properties of the contractile apparatus such as sensitivity to Ca 2+ [9], pH sensitivity of contraction [10], sarcomere length sensing [11] and rigor cross-bridge-activated optimal tension [12]. Although the current knowledge gives no indication that MHC and TnC share a structural relationship, the polymorphic nature of these proteins coupled with compelling evidence that the function of each one is influenced by the actions of the other suggests that mammalian skeletal-muscle fibres may contain specific combinations of TnC and MHC isoforms.…”

Section: Introductionmentioning

confidence: 99%

A single-fibre study of the relationship between MHC and TnC isoform composition in rat skeletal muscle

O'Connell

Nguyễn

Stephenson

2004

Biochemical Journal

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In the present study, we investigated the possibility that MHC (myosin heavy chain) and TnC (troponin C) isoforms exist in specific combinations in rat-skeletal-muscle fibres. Single fibres (numbering 245) from soleus (predominantly slow-twitch) and sternomastoid (predominantly fast-twitch) muscles of adult rats were analysed for MHC and TnC isoform composition, using alanine-SDS/PAGE for separating MHC isoforms, and a novel method (based on the previously reported influence of Ca2+ on the mobility of Ca2+-binding proteins in SDS gels) for unequivocal identification of TnC isoforms in single-fibre segments. In this study, all fibres that contained only one MHC isoform (slow or fast) contained only the matching TnC isoform and all fibres that contained multiple fast MHC isoforms contained only the fast TnC isoform. Fibres expressing both slow and fast MHC isoforms displayed either both TnC isoforms or only one TnC isoform of a type depending on the relative proportion of fast/slow MHC present. Our results suggest a close relationship between MHC and TnC isoform composition in non-transforming skeletal muscles of adult rat.

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The Cardiac Troponin C Isoform and the Length Dependence of Ca2+Sensitivity of Tension in Myocardium

Cited by 15 publications

References 5 publications

Acute effects of pulmonary artery banding in sheep on right ventricle pressure–volume relations: relevance to the arterial switch operation

Acute effects of pulmonary artery banding in sheep on right ventricle pressure–volume relations: relevance to the arterial switch operation

Strong Binding of Myosin Modulates Length-Dependent Ca ²⁺ Activation of Rat Ventricular Myocytes

A single-fibre study of the relationship between MHC and TnC isoform composition in rat skeletal muscle

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The Cardiac Troponin C Isoform and the Length Dependence of Ca2+Sensitivity of Tension in Myocardium

Cited by 15 publications

References 5 publications

Acute effects of pulmonary artery banding in sheep on right ventricle pressure–volume relations: relevance to the arterial switch operation

Acute effects of pulmonary artery banding in sheep on right ventricle pressure–volume relations: relevance to the arterial switch operation

Strong Binding of Myosin Modulates Length-Dependent Ca 2+ Activation of Rat Ventricular Myocytes

A single-fibre study of the relationship between MHC and TnC isoform composition in rat skeletal muscle

Contact Info

Product

Resources

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Strong Binding of Myosin Modulates Length-Dependent Ca ²⁺ Activation of Rat Ventricular Myocytes