Stretch modulation of cardiac contractility: importance of myocyte calcium during the slow force response

Kaur, Sarbjot; Shen, Xin Ming; Power, Amelia; Ward, Marie‐Louise

doi:10.1007/s12551-020-00615-6

Cited by 13 publications

(12 citation statements)

References 77 publications

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“…The slow response is a graduate increase in twitch amplitude upon a stretch of a cardiac muscle. These and other authors concluded that that the strain dependence of Na + -H + exchange is a major contributor to the slow response [31,32]. We show here that the simplest assumption (6A) is sufficient for explaining the amplitude and the time course of the slow responses of the twitch amplitude and Ca 2+ transients to an increase in muscle preload.…”

Section: Plos Onesupporting

confidence: 61%

Computationally efficient model of myocardial electromechanics for multiscale simulations

2021

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A model of myocardial electromechanics is suggested. It combines modified and simplified versions of previously published models of cardiac electrophysiology, excitation-contraction coupling, and mechanics. The mechano-calcium and mechano-electrical feedbacks, including the strain-dependence of the propagation velocity of the action potential, are also accounted for. The model reproduces changes in the twitch amplitude and Ca2+-transients upon changes in muscle strain including the slow response. The model also reproduces the Bowditch effect and changes in the twitch amplitude and duration upon changes in the interstimulus interval, including accelerated relaxation at high stimulation frequency. Special efforts were taken to reduce the stiffness of the differential equations of the model. As a result, the equations can be integrated numerically with a relatively high time step making the model suitable for multiscale simulation of the human heart and allowing one to study the impact of myocardial mechanics on arrhythmias.

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Section: Plos Onesupporting

confidence: 61%

Computationally efficient model of myocardial electromechanics for multiscale simulations

2021

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“…The other study was perfomed by Rysä et al . 4 and investigated the response of cardiomyocytes to mechanical stretch, which is known to cause Ca 2+ influx 40 , 41 due to compromised membrane integrity 42 – 45 . The nature of the meta-analysis not only allows for greater power to detect differential expression and associated pathways 46 , but also questions the conserved nature of the transcriptomic response across different cell and injury types.…”

Section: Resultsmentioning

confidence: 99%

Short-term transcriptomic response to plasma membrane injury

Häger

Dias

Sønder

et al. 2021

Sci Rep

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Plasma membrane repair mechanisms are activated within seconds post-injury to promote rapid membrane resealing in eukaryotic cells and prevent cell death. However, less is known about the regeneration phase that follows and how cells respond to injury in the short-term. Here, we provide a genome-wide study into the mRNA expression profile of MCF-7 breast cancer cells exposed to injury by digitonin, a mild non-ionic detergent that permeabilizes the plasma membrane. We focused on the early transcriptional signature and found a time-dependent increase in the number of differentially expressed (> twofold, P < 0.05) genes (34, 114 and 236 genes at 20-, 40- and 60-min post-injury, respectively). Pathway analysis highlighted a robust and gradual three-part transcriptional response: (1) prompt activation of immediate-early response genes, (2) activation of specific MAPK cascades and (3) induction of inflammatory and immune pathways. Therefore, plasma membrane injury triggers a rapid and strong stress and immunogenic response. Our meta-analysis suggests that this is a conserved transcriptome response to plasma membrane injury across different cell and injury types. Taken together, our study shows that injury has profound effects on the transcriptome of wounded cells in the regeneration phase (subsequent to membrane resealing), which is likely to influence cellular status and has been previously overlooked.

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“…A potential mechanism for the slow force response has been suggested, including the activation of stretch-activated non-specific cation channels and paracrine/autocrine signaling. The slow force response has been shown to be helpful in normal function and detrimental in diseases such as heart failure [ 21 ]. In the rapid response, when the heart muscle is stretched, there is an increase in force seen in the same action potential.…”

Section: Discussionmentioning

confidence: 99%

X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin

Limbu

Prosser

Lederer

et al. 2021

Cells

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The stretching of a cardiomyocyte leads to the increased production of reactive oxygen species that increases ryanodine receptor open probability through a process termed X-ROS signaling. The stretching of the myocyte also increases the calcium affinity of myofilament Troponin C, which increases its calcium buffering capacity. Here, an integrative experimental and modeling study is pursued to explain the interplay of length-dependent changes in calcium buffering by troponin and stretch-activated X-ROS calcium signaling. Using this combination, we show that the troponin C-dependent increase in myoplasmic calcium buffering during myocyte stretching largely offsets the X-ROS-dependent increase in calcium release from the sarcoplasmic reticulum. The combination of modeling and experiment are further informed by the elimination of length-dependent changes to troponin C calcium binding in the presence of blebbistatin. Here, the model suggests that it is the X-ROS signaling-dependent Ca2+ release increase that serves to maintain free myoplasmic calcium concentrations during a change in myocyte length. Together, our experimental and modeling approaches have further defined the relative contributions of X-ROS signaling and the length-dependent calcium buffering by troponin in shaping the myoplasmic calcium transient.

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Stretch modulation of cardiac contractility: importance of myocyte calcium during the slow force response

Cited by 13 publications

References 77 publications

Computationally efficient model of myocardial electromechanics for multiscale simulations

Computationally efficient model of myocardial electromechanics for multiscale simulations

Short-term transcriptomic response to plasma membrane injury

X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin

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