Different Myofilament Nearest-Neighbor Interactions Have Distinctive Effects on Contractile Behavior

Razumova, Maria V.; Bukatina, Anna E.; Campbell, Kenneth B.

doi:10.1016/s0006-3495(00)76849-4

Cited by 102 publications

(143 citation statements)

References 44 publications

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“…These dynamic dimensions of functional differences would be expected to compliment the species-specific resting heart rate (600 beats/min in the mouse vs. 300 beats/min in the rat) because the dynamic response of cardiac muscle contraction involves interactive feedback between the thin filament-activating effects of Tn and MHC cycling kinetics (4,6,14,26). Therefore, changes in the composition of MHC and Tn, as in hearts of different species, will likely impact the overall dynamic response of the heart.…”

Section: Discussionmentioning

confidence: 99%

“…In mouse and rat fibers, cooperatively coupled effects on the recruitment dynamics may be different due to variation in either MHC or Tn or both. The Hill coefficient, n, which is an aggregate measure of cooperativity in Ca 2ϩ binding to Tn and near-neighbor interactions between Tn-Tn, XB-Tn, and XB-XB (6,26), was significantly lower in mouse fibers (Tables 1-4). Because XB-related cooperativity has the greatest impact on length-mediated XB recruitment dynamics (6), subtle changes in the strength of such cooperativity could have major implications for differences in the XB recruitment dynamics of mouse and rat cardiac muscle fibers.…”

Section: Sequence Heterogeneity In Cardiac Tn Isoforms: Implications mentioning

confidence: 99%

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Interaction between myosin heavy chain and troponin isoforms modulate cardiac myofiber contractile dynamics

Chandra

Tschirgi²,

Ford³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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117

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Chandra M, Tschirgi ML, Ford SJ, Slinker BK, Campbell KB. Interaction between myosin heavy chain and troponin isoforms modulate cardiac myofiber contractile dynamics. Am J Physiol Regul Integr Comp Physiol 293: R1595-R1607, 2007. First published July 11, 2007; doi:10.1152/ajpregu.00157.2007.-Coordinated expression of species-specific myosin heavy chain (MHC) and troponin (Tn) isoforms may bring about a dynamic complementarity to match muscle contraction speed with species-specific heart rates. Contractile system function and dynamic force-length measurements were made in muscle fibers from mouse and rat hearts and in muscle fibers after reconstitution with either recombinant homologous Tn or orthologous Tn. The rate constants of length-mediated cross-bridge (XB) recruitment (b) and tension redevelopment (k tr) of mouse fibers were significantly faster than those of rat fibers. Both the tension cost (ATPase/tension) and rate constant of length-mediated XB distortion (c) were higher in the mouse than in the rat. Thus the mouse fiber was faster in all dynamic and functional aspects than the rat fiber. Mouse Tn significantly increased b and k tr in rat fibers; conversely, rat Tn significantly decreased b and k tr in mouse fibers. Thus the lengthmediated recruitment of force-bearing XB occurs much more rapidly in the presence of mouse Tn than in the presence of rat Tn, demonstrating that the speed of XB recruitment is regulated by Tn. There was a significant interaction between Tn and MHC such that changes in either Tn or MHC affected the speed of XB recruitment. Our data demonstrate that the dynamics of myocardial contraction are different in the mouse and rat hearts because of sequence heterogeneity in MHC and Tn. At the myofilament level, coordinated expression of complementary regulatory contractile proteins produces a functional dynamic phenotype that allows the cardiovascular systems to function effectively at different heart rates. myofiber dynamics; contraction speed; heart rate THERE IS SUBSTANTIAL PROTEIN sequence heterogeneity among orthologous cardiac myosin heavy chain (MHC) and troponin (Tn) isoforms across different animal species (30). This sequence heterogeneity in regulatory contractile proteins significantly affects myofilament dynamics, as assessed by the force response to muscle length change in constantly activated cardiac myofibers, which exhibits two clearly separable processes (3,5,20,30,35): 1) a relatively fast force dynamic associated with myosin cross-bridge (XB) distortion and 2) a relatively slow force dynamic associated with recruitment of additional XB into force-bearing states. The dynamics of XB distortion are principally determined by the enzymatic kinetics of MHC, and the dynamics of XB recruitment are affected greatly by cooperative interactions between Tn actions and XB cycling kinetics (3, 5, 6, 30).Our group (9) recently showed that differences in troponin T (TnT), a subunit of the Tn regulatory protein complex, affected the slow XB recruitment dynamic (9), whereas a shift f...

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Section: Discussionmentioning

confidence: 99%

Section: Sequence Heterogeneity In Cardiac Tn Isoforms: Implications mentioning

confidence: 99%

Interaction between myosin heavy chain and troponin isoforms modulate cardiac myofiber contractile dynamics

Chandra

Tschirgi²,

Ford³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

117

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“…The basis for the present model was developed in earlier publications (5,6,23,24) where the origin of constantly activated myocardial dynamics was considered to arise from the myofilament kinetic scheme shown in Fig. 1.…”

Section: Model Developmentmentioning

confidence: 99%

“…1) and kinetic-modifying features were used to derive a set of equations for a general dynamic forcelength relation, the resulting equation set was highly nonlinear, of high dynamic order, and contained many parameters (5,6,24). To give such complicated equations some practical utility, we applied linearization and model-order reduction techniques to form a simplified recruitment-distortion model.…”

Section: Model Developmentmentioning

confidence: 99%

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Interpreting cardiac muscle force-length dynamics using a novel functional model

Campbell

Chandra²,

Kirkpatrick³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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173

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. Interpreting cardiac muscle force-length dynamics using a novel functional model. Am J Physiol Heart Circ Physiol 286: H1535-H1545, 2004; 10.1152/ ajpheart.01029.2003.-To describe the dynamics of constantly activated cardiac muscle, we propose that length affects force via both recruitment and distortion of myosin cross bridges. This hypothesis was quantitatively tested for descriptive and explanative validity. Skinned cardiac muscle fibers from animals expressing primarily ␣-myosin heavy chain (MHC) (mouse, rat) or ␤-MHC (rabbit, ferret) were activated with solutions from pCa 6.1 to 4.3. Activated fibers were subjected to small-amplitude length perturbations [⌬L(t)] rich in frequency content between 0.1 and 40 Hz. In descriptive validation tests, the model was fit to the ensuing force response [⌬F(t)] in the time domain. In fits to 118 records, the model successfully accounted for most of the measured variation in ⌬F(t) (R 2 range, 0.997-0.736; median, 0.981). When some residual variations in ⌬F(t) were not accounted for by the model (as at low activation), there was very little coherence (Ͻ0.5) between these residual force variations and the applied ⌬L(t) input function, indicating that something other than ⌬L(t) was causing the measured variation in ⌬F(t). With one exception, model parameters were estimated with standard errors on the order of 1% or less. Thus parameters of the recruitment component of the model could be uniquely separated from parameters of the distortion component of the model and parameters estimated from any given fiber could be considered unique to that fiber. In explanative validation tests, we found that recruitment and distortion parameters were positively correlated with independent assessments of the physiological entity they were assumed to represent. The recruitment distortion model was judged to be valid from both descriptive and explanative perspectives and is, therefore, a useful construct for describing and explaining dynamic force-length relationships in constantly activated cardiac muscle. muscle stiffness; cross-bridge recruitment; cross-bridge distortion; model validation; mouse; rat; ferret; rabbit MUSCLE LENGTH modulates cardiac muscle force development, and the resultant force-length relationship (FLR) is basic to the Frank-Starling mechanism of the heart. In general, however, muscle FLRs extend beyond the typical isometric twitching conditions under which force-length data are commonly collected to also include the force response to any length change during contraction. Thus descriptors of muscle FLR should also depict the dynamic force response to length changes that occur during contraction. One often-studied aspect of the dynamic FLR is the force response to sinusoidal length change in a constantly activated muscle fiber. Under these dynamic conditions, the amplitude and phase of the force response depends on both the frequency and amplitude of the sinusoidal length change. Dividing the steady-state sinusoidal force response by the sinusoidal length change yields...

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Varying thin filament activation in the framework of the Huxley'57 model

Kimmig

Caruel

Chapelle

2022

Numer Methods Biomed Eng

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Muscle contraction is triggered by the activation of the actin sites of the thin filament by calcium ions. It results that the thin filament activation level varies over time. Moreover, this activation process is also used as a regulation mechanism of the developed force. Our objective is to build a model of varying actin site activation level within the classical Huxley'57 two-state framework. This new model is obtained as an enhancement of a previously proposed formulation of the varying thick filament activation within the same framework [1]. We assume that the state of an actin site depends on whether it is activated and whether it forms a cross-bridge with the associated myosin head, which results in four possible states. The transitions between the actin site states are controlled by the global actin sites activation level and the dynamics of these transitions is coupled with the attachment-detachment process. A preliminary calibration of the model with experimental twitch contraction data obtained at varying sarcomere lengths is performed.

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Different Myofilament Nearest-Neighbor Interactions Have Distinctive Effects on Contractile Behavior

Cited by 102 publications

References 44 publications

Interaction between myosin heavy chain and troponin isoforms modulate cardiac myofiber contractile dynamics

Interaction between myosin heavy chain and troponin isoforms modulate cardiac myofiber contractile dynamics

Interpreting cardiac muscle force-length dynamics using a novel functional model

Varying thin filament activation in the framework of the Huxley'57 model

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