Extensive eccentric contractions in intact cardiac trabeculae: revealing compelling differences in contractile behaviour compared to skeletal muscles

Tomalka, André; Röhrle, Oliver; Han, June‐Chiew; Pham, Toan; Taberner, Andrew J.; Siebert, Tobias

doi:10.1098/rspb.2019.0719

Cited by 19 publications

(8 citation statements)

References 79 publications

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“…Cardiac muscles are not stretched while contracting in vivo, and thus a residual force enhancement caused by a Ca 2+ -dependent increase in titin stiffness would not play a physiological role during contractions. This interpretation is strengthened by a recent study showing that intact cardiac trabeculae also do not present the residual force enhancement after stretch 25 .…”

Section: Discussionmentioning

confidence: 74%

Force enhancement after stretch of isolated myofibrils is increased by sarcomere length non-uniformities

Haeger

Rassier

2020

Sci Rep

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When a muscle is stretched during a contraction, the resulting steady-state force is higher than the isometric force produced at a comparable sarcomere length. This phenomenon, also referred to as residual force enhancement, cannot be readily explained by the force-sarcomere length relation. One of the most accepted mechanisms for the residual force enhancement is the development of sarcomere length non-uniformities after an active stretch. The aim of this study was to directly investigate the effect of non-uniformities on the force-producing capabilities of isolated myofibrils after they are actively stretched. We evaluated the effect of depleting a single A-band on sarcomere length non-uniformity and residual force enhancement. We observed that sarcomere length non-uniformity was effectively increased following A-band depletion. Furthermore, isometric forces decreased, while the percent residual force enhancement increased compared to intact myofibrils (5% vs. 20%). We conclude that sarcomere length non-uniformities are partially responsible for the enhanced force production after stretch.

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Section: Discussionmentioning

confidence: 74%

Force enhancement after stretch of isolated myofibrils is increased by sarcomere length non-uniformities

Haeger

Rassier

2020

Sci Rep

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“…Whether the reduction in passive stress can be attributed to the reported reduced diastolic Ca 2+ following detubulation 30,31 remains uncertain, as a change in passive stress is typically attributed to altered titin stiffness. We do not expect acute detubulation to alter titin stiffness, but there have been studies suggesting that the interaction between titin and actin is Ca 2+ concentration‐dependent, 56 and such interaction is high at diastole 57 …”

Section: Discussionmentioning

confidence: 95%

“…We do not expect acute detubulation to alter titin stiffness, but there have been studies suggesting that the interaction between titin and actin is Ca 2+ concentration-dependent, 56 and such interaction is high at diastole. 57 Detubulation not only reduced stress at L o , it also lowered the stress-length relation, both the total (end-systolic) stress-length and passive stress-length relations ( Figure 4A). The lower slopes of both the isometric and the work-loop end-systolic stress-length relations following detubulation indicate that muscle contractility was reduced.…”

Section: Mechanical Consequences Of Detubulationmentioning

confidence: 90%

Disruption of transverse‐tubular network reduces energy efficiency in cardiac muscle contraction

et al. 2020

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Aim Altered organization of the transverse‐tubular network is an early pathological event occurring even prior to the onset of heart failure. Such t‐tubular remodelling disturbs the synchrony and signalling between membranous and intracellular ion channels, exchangers, receptors and ATPases essential in the dynamics of excitation‐contraction coupling, leading to ionic abnormality and mechanical dysfunction in heart disease progression. In this study, we investigated whether a disrupted t‐tubular network has a direct effect on cardiac mechano‐energetics. Our aim was to understand the fundamental link between t‐tubular remodelling and impaired energy metabolism, both of which are characteristics of heart failure. We thus studied healthy tissue preparations in which cellular processes are not altered by any disease event. Methods We exploited the “formamide‐detubulation” technique to acutely disrupt the t‐tubular network in rat left‐ventricular trabeculae. We assessed the energy utilization by cellular Ca2+ cycling and by crossbridge cycling, and quantified the change of energy efficiency following detubulation. For these measurements, trabeculae were mounted in a microcalorimeter where force and heat output were simultaneously measured. Results Following structural disorganization from detubulation, muscle heat output associated with Ca2+ cycling was reduced, indicating impaired intracellular Ca2+ homeostasis. This led to reduced force production and heat output by crossbridge cycling. The reduction in force‐length work was not paralleled by proportionate reduction in the heat output and, as such, energy efficiency was reduced. Conclusions These results reveal the direct energetic consequences of disrupted t‐tubular network, linking the energy disturbance and the t‐tubular remodelling typically observed in heart failure.

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“…Muscle preparation, storage and activation techniques for permeabilized single muscle fibers were in line with Tomalka et al, 2017 , 2019 . Briefly, muscle fibers were extracted from seven freshly killed male Wistar rats (3–7 months, 425–500 g, cage-sedentary, 12 h:12 h light: dark cycle, housing-temperature: 22°C).…”

Section: Methodsmentioning

confidence: 99%

Cross-Bridges and Sarcomeric Non-cross-bridge Structures Contribute to Increased Work in Stretch-Shortening Cycles

et al. 2020

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Stretch-shortening cycles (SSCs) refer to the muscle action when an active muscle stretch is immediately followed by active muscle shortening. This combination of eccentric and concentric contractions is the most important type of daily muscle action and plays a significant role in natural locomotion such as walking, running or jumping. SSCs are used in human and animal movements especially when a high movement speed or economy is required. A key feature of SSCs is the increase in muscular force and work during the concentric phase of a SSC by more than 50% compared with concentric muscle actions without prior stretch (SSC-effect). This improved muscle capability is related to various mechanisms, including pre-activation, stretch-reflex responses and elastic recoil from serial elastic tissues. Moreover, it is assumed that a significant contribution to enhanced muscle capability lies in the sarcomeres itself. Thus, we investigated the force output and work produced by single skinned fibers of rat soleus muscles during and after ramp contractions at a constant velocity. Shortening, lengthening, and SSCs were performed under physiological boundary conditions with 85% of the maximum shortening velocity and stretch-shortening magnitudes of 18% of the optimum muscle length. The different contributions of cross-bridge (XB) and non-cross-bridge (non-XB) structures to the total muscle force were identified by using Blebbistatin. The experiments revealed three main results: (i) partial detachment of XBs during the eccentric phase of a SSC, (ii) significantly enhanced forces and mechanical work during the concentric phase of SSCs compared with shortening contractions with and without XB-inhibition, and (iii) no residual force depression after SSCs. The results obtained by administering Blebbistatin propose a titin-actin interaction that depends on XB-binding or active XB-based force production. The findings of this study further suggest that enhanced forces generated during the active lengthening phase of SSCs persist during the subsequent shortening phase, thereby contributing to enhanced

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Extensive eccentric contractions in intact cardiac trabeculae: revealing compelling differences in contractile behaviour compared to skeletal muscles

Cited by 19 publications

References 79 publications

Force enhancement after stretch of isolated myofibrils is increased by sarcomere length non-uniformities

Force enhancement after stretch of isolated myofibrils is increased by sarcomere length non-uniformities

Disruption of transverse‐tubular network reduces energy efficiency in cardiac muscle contraction

Cross-Bridges and Sarcomeric Non-cross-bridge Structures Contribute to Increased Work in Stretch-Shortening Cycles

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