Cardiac Length Dependence of Force and Force Redevelopment Kinetics with Altered Cross-Bridge Cycling

Adhikari, Bishow; Regnier, Michael; Rivera, Anthony J.; Kreutziger, Kareen L.; Martyn, Donald A.

doi:10.1529/biophysj.103.039131

Cited by 68 publications

(96 citation statements)

References 44 publications

(74 reference statements)

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“…The positive sigmoidal relationship between k tr and pCa in the preparations from the 4 and 17°C groups indicates that the rate of myofilament activation increases with Ca 2+ concentration. This is the typical response of mammalian trabeculae to increasing Ca 2+ and is interpreted as an increase in the transition from non-force-to force-generating crossbridges (Wolff et al, 1995;Adhikari et al, 2004;Gillis et al, 2007). In contrast, the comparatively flat response of the preparations from the 11°C group suggests that the rate of cross-bridge cycling is similar at all activation pCa values.…”

Section: Discussionmentioning

confidence: 90%

Cold acclimation increases cardiac myofilament function and ventricular pressure generation in trout

Klaiman

Pyle

Gillis

2014

Journal of Experimental Biology

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Reducing temperature below the optimum of most vertebrate hearts impairs contractility and reduces organ function. However, a number of fish species, including the rainbow trout, can seasonally acclimate to low temperature. Such ability requires modification of physiological systems to compensate for the thermodynamic effects of temperature on biological processes. The current study tested the hypothesis that rainbow trout compensate for the direct effect of cold temperature by increasing cardiac contractility during cold acclimation. We examined cardiac contractility, following thermal acclimation (4, 11 and 17°C), by measuring the Ca 2+ sensitivity of force generation by chemically skinned cardiac trabeculae as well as ventricular pressure generation using a modified Langendorff preparation. We demonstrate, for the first time, that the Ca 2+ sensitivity of force generation was significantly higher in cardiac trabeculae from 4°C-acclimated trout compared with those acclimated to 11 or 17°C, and that this functional change occurred in parallel with a decrease in the level of cardiac troponin T phosphorylation. In addition, we show that the magnitude and rate of ventricular pressure generation was greater in hearts from trout acclimated to 4°C compared with those from animals acclimated to 11 or 17°C. Taken together, these results suggest that enhanced myofilament function, caused by modification of existing contractile proteins, is at least partially responsible for the observed increase in pressure generation after acclimation to 4°C. In addition, by examining the phenotypic plasticity of a comparative model we have identified a strategy, used in vivo, by which the force-generating capacity of cardiac muscle can be increased.

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Section: Discussionmentioning

confidence: 90%

Cold acclimation increases cardiac myofilament function and ventricular pressure generation in trout

Klaiman

Pyle

Gillis

2014

Journal of Experimental Biology

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“…The Ca 2ϩ -dependent increase in k tr was observed for both skeletal and cardiac muscle. In skeletal muscle k tr increases ϳ10-fold from low to high levels of Ca 2ϩ concentration with a curvilinear k tr vs. relative force relationship (13), whereas in cardiac muscle k tr increases ϳ2-to 5-fold (1,13,28,46) with either a linear (35,46) or a curvilinear (1,28,30) k tr vs. force relationship. In our study, the k tr values for the unextracted trabeculae increased approximately threefold with increasing levels of Ca 2ϩ concentration and the k tr vs. relative force relationship was linear.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the rate of cardiac muscle contraction by troponin C constructs with various calcium binding affinities

Norman¹,

Rall²,

Tikunova³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Norman C, Rall JA, Tikunova SB, Davis JP. Modulation of the rate of cardiac muscle contraction by troponin C constructs with various calcium binding affinities. Am J Physiol Heart Circ Physiol 293: H2580-H2587, 2007. First published August 10, 2007; doi:10.1152/ajpheart.00039.2007.-We investigated whether changing thin filament Ca 2ϩ sensitivity alters the rate of contraction, either during normal cross-bridge cycling or when cross-bridge cycling is increased by inorganic phosphate (P i). We increased or decreased Ca 2ϩ sensitivity of force production by incorporating into rat skinned cardiac trabeculae the troponin C (TnC) mutants V44QTnCF27W and F20QTnCF27W . The rate of isometric contraction was assessed as the rate of force redevelopment (ktr) after a rapid release and restretch to the original length of the muscle. Both in the absence of added Pi and in the presence of 2.5 mM added Pi F27W . This study suggests that TnC Ca 2ϩ binding properties modulate the rate of cardiac muscle contraction at submaximal levels of Ca 2ϩ activation. This result has physiological relevance considering that, on a beat-to-beat basis, the heart contracts at submaximal Ca 2ϩ activation.force; thin filament CARDIAC MUSCLE CONTRACTION is initiated by Ca 2ϩ binding to troponin C (TnC), which triggers conformational changes on the thin filament, exposing myosin-binding sites on actin. After the myosin heads (cross bridges) attach to actin, the thin filaments slide along the thick filaments and the muscle contracts (18). The kinetics of cross-bridge cycling can be studied with several approaches. One approach has been developed by Brenner (3, 4). According to this protocol, a rapid shorteningrestretch maneuver mechanically detaches the cross bridges, and the rate at which the cross bridges reattach and generate force is a measure of the rate of contraction, known as the rate of force (tension) redevelopment (k tr ).In both cardiac and skeletal muscle, it is well established that k tr becomes faster with increasing levels of activation by Ca 2ϩ (5,6,13,28,46). Many studies have investigated the role Ca 2ϩ plays in the activation dependence of k tr (for review, see Ref. 13). It has been proposed that the effects of Ca 2ϩ on k tr occur either as a direct effect of Ca 2ϩ on the cross bridges or indirectly by activation of the thin filament, which subsequently allows cross bridges to cycle from non-force-generating states to force-generating states. Studies in skeletal muscle investigated the hypothesis that Ca 2ϩ has a direct effect on the cross bridge cycle. Caged inorganic phosphate (P i ) experiments suggest that Ca 2ϩ does not regulate the kinetics of P i release but rather the distribution of cross bridges between non-force-generating and force-generating states (25,45). Similarly, in vitro motility assays have shown that Ca 2ϩ , through binding to TnC, controls the number of cross bridges interacting with actin rather than directly controlling the rate of ATP hydrolysis or the filament sliding speed (14, 17). Moreover, Ca 2ϩ does...

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“…Whole cTn complexes were formed using rat cTnC (WT or cTnC IANBD C35S ), rat cTnI (WT, WT-Ser(P)-23/Ser(P)-24, WT-S23D/S24D, R146G, R146G/Ser(P)-23/Ser(P)-24, R21C, or R21C/S23D/S24D), and rat cTnT (WT) at a 1:1:1 molar ratio and then dialyzed through a series of buffers with gradually decreased KCl concentration at 4°C (without stirring) as described previously (38,39 fluorescence experiments were measured using an LS50B luminescence spectrometer (PerkinElmer Life Sciences) at 15°C as described previously (7,36,40 (43). After this, both ventricles were cut open, and the whole heart was demembranated in skinning solution containing (in mM): 100 KCl, 9 MgCl 2 , 4 Na 2 ATP, 5 K 2 EGTA, 10 MOPS, 1% Triton X-100, pH 7.0, 50% v/v glycerol, and 1:100 dilution "protease inhibitor mixture" (Sigma, catalog no.…”

Section: Methodsmentioning

confidence: 99%

Troponin I Mutations R146G and R21C Alter Cardiac Troponin Function, Contractile Properties, and Modulation by Protein Kinase A (PKA)-mediated Phosphorylation

Cheng

Rao

et al. 2015

Journal of Biological Chemistry

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Background: R146G and R21C mutations in cardiac TnI are associated with hypertrophic cardiomyopathy. Results: Both mutations blunt PKA-mediated effects on weakening cTnI-cTnC interaction and accelerating myofibril relaxation. Conclusion: Both mutations result in hypercontraction and impaired relaxation, which may contribute to increased risk to traumatic heart failure. Significance: This study increases mechanistic understanding of how single amino acid mutations result in cardiac contractile dysfunction.

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Cardiac Length Dependence of Force and Force Redevelopment Kinetics with Altered Cross-Bridge Cycling

Cited by 68 publications

References 44 publications

Cold acclimation increases cardiac myofilament function and ventricular pressure generation in trout

Cold acclimation increases cardiac myofilament function and ventricular pressure generation in trout

Modulation of the rate of cardiac muscle contraction by troponin C constructs with various calcium binding affinities

Troponin I Mutations R146G and R21C Alter Cardiac Troponin Function, Contractile Properties, and Modulation by Protein Kinase A (PKA)-mediated Phosphorylation

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