Differential contribution of cardiac sarcomeric proteins in the myofibrillar force response to stretch

Mou, Younss Aït; Guennec, J.-Y. Le; Mosca, Emilio; Tombe, Pieter P. de; Cazorla, Olivier

doi:10.1007/s00424-008-0501-x

Cited by 38 publications

(36 citation statements)

References 51 publications

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“…Sustained stretch of cardiac muscle may lead to altered protein kinase activity(16)(2), which could alter twitch kinetics. To address this, we examined twitch kinetic parameters (activation time, relaxation time, and total duration) at the 10%, 50%, and 75% twitch force level during the SFR protocol.…”

Section: Resultsmentioning

confidence: 99%

“…Another proposed mechanism involves local release of Angiotensin-II that, following several proposed signal transduction steps, modulates the activity of the Na + /H + exchanger to, likewise, induce an increase in cellular Ca 2+ load via the sarcolemmal Na + /Ca 2+ exchange membrane carrier, although this hypothesis is not universally supported(22). Finally, stretch has also been proposed to increase protein kinase activity that may alter cardiac EC-coupling in addition to alterations of contractile protein phosphorylation (16)(2). …”

Section: Introductionmentioning

confidence: 99%

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Impact of titin strain on the cardiac slow force response

Ait-Mou

Zhang

Martin

et al. 2017

Progress in Biophysics and Molecular Biology

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Stretch of myocardium, such as occurs upon increased filling of the cardiac chamber, induces two distinct responses: an immediate increase in twitch force followed by a slower increase in twitch force that develops over the course of several minutes. The immediate response is due, in part, to modulation of myofilament Ca2+ sensitivity by sarcomere length (SL). The slowly developing force response, termed the Slow Force Response (SFR), is caused by a slowly developing increase in intracellular Ca2+ upon sustained stretch. A blunted immediate force response was recently reported for myocardium isolated from homozygous giant titin mutant rats (HM) compared to muscle from wild-type littermates (WT). Here, we examined the impact of titin isoform on the SFR. Right ventricular trabeculae were isolated and mounted in an experimental chamber. SL was measured by laser diffraction. The SFR was recorded in response to a 0.2 μm SL stretch in the presence of [Ca2+]o=0.4 mM, a bathing concentration reflecting ~50% of maximum twitch force development at 25 °C. Presence of the giant titin isoform (HM) was associated with a significant reduction in diastolic passive force upon stretch, and ~50% reduction of the magnitude of the SFR; the rate of SFR development was unaffected. The sustained SL stretch was identical in both muscle groups. Therefore, our data suggest that cytoskeletal strain may underlie directly the cellular mechanisms that lead to the increased intracellular [Ca2+]i that causes the SFR, possibly by involving cardiac myocyte integrin signaling pathways.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of titin strain on the cardiac slow force response

Ait-Mou

Zhang

Martin

et al. 2017

Progress in Biophysics and Molecular Biology

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“…Thus, when sarcomeres are stretched the myofilaments produce more force for the same level of calcium [2, 3, 5], i.e., the myofilaments display length-dependent activation (LDA). Multiple proteins have been proposed to mediate LDA such as the thin-filament based troponin (Tn) complex[1, 8], with a central role likely played by threonine 144 of cTnI[9], the thick-filament based proteins cMyBP-C and MLC2 [10, 11], and titin, the third myofilament of the cardiac sarcomere [8, 12–16]. Titin is an attractive candidate because it constitutes the only filament that directly senses stretch and that interacts with both actin and myosin[17].…”

Section: Introductionmentioning

confidence: 99%

Calcium sensitivity and the Frank–Starling mechanism of the heart are increased in titin N2B region-deficient mice

Lee

Peng

Radkë

et al. 2010

Journal of Molecular and Cellular Cardiology

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Previous work suggests that titin-based passive tension is a factor in the Frank-Starling mechanism of the heart, by increasing length-dependent activation (LDA) through an increase in calcium sensitivity at long sarcomere length. We tested this hypothesis in a mouse model (N2B KO model) in which titin-based passive tension is elevated as a result of the excision of the N2B element, one of cardiac titin's spring elements. LDA was assessed by measuring the active tension-pCa (−log[Ca 2+ ]) relationship at sarcomere length (SLs) of 1.95, 2.10 and 2.30 µm in WT and N2B KO skinned myocardium. LDA was positively correlated with titin-based passive tension, due to an increase in calcium sensitivity at the longer SLs in the KO. For example, at pCa 6.0 the KO:WT tension ratio was 1.28 ± 0.07 and 1.42 ± 0.04 at SLs of 2.1 and 2.3 µm, respectively. There was no difference in protein expression or phosphorylation of sarcomeric proteins. We also measured the calcium sensitivity after PKA treating the skinned muscle and found that titin-based passive tension was also now correlated with LDA, with a slope that was significantly increased compared to no PKA treatment. Finally, we performed isolated heart experiments and measured the Frank-Starling relation (slope of developed wall stress-LV volume relation) as well as diastolic stiffness (slope of diastolic wall stress -volume relation). The FSM was more pronounced in the N2B KO hearts and the slope of the FSM correlated with diastolic stiffness. These findings support that titin-based passive tension triggers an increase in calcium sensitivity at long sarcomere length, thereby playing an important role in the Frank-Starling mechanism of the heart.

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“…For example, at large sarcomere lengths, pCa 50 and maximum tension were significantly higher in sub-endocardial cell preparations compared to sub-epicardial cell preparations. 1 Furthermore, with increases in sarcomere length, n H increased in sub-endocardial preparations but decreased in sub-epicardial, and the magnitude of the length-dependent response of pCa 50 and k tr was greater in sub-endocardial cells. 1 To better account for and quantify the effect of ventricular wall location on sarcomere structure, properties, and performance, measurements should be taken at multiple sarcomere lengths, with and without trypsin degradation of titin, and from additional locations within the ventricular wall.…”

Section: Structurementioning

confidence: 90%

“…1,8,16 In particular, active and passive tension is greater in sub-endocardial cells, 9 which may be due to differences in sarcomere rest length and subsequently different levels of titin and collagen loading. In support of this suggestion, Chung and Granzier 11 found that the working sarcomere length range was smaller in sub-epicardial cells.…”

Section: Structurementioning

confidence: 99%

Cardiac Tissue Structure, Properties, and Performance: A Materials Science Perspective

2014

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From an engineering perspective, many forms of heart disease can be thought of as a reduction in biomaterial performance, in which the biomaterial is the tissue comprising the ventricular wall. In materials science, the structure and properties of a material are recognized to be interconnected with performance. In addition, for most measurements of structure, properties, and performance, some processing is required. Here, we review the current state of knowledge regarding cardiac tissue structure, properties, and performance as well as the processing steps taken to acquire those measurements. Understanding the impact of these factors and their interactions may enhance our understanding of heart function and heart failure. We also review design considerations for cardiac tissue property and performance measurements because, to date, most data on cardiac tissue has been obtained under non-physiological loading conditions. Novel measurement systems that account for these design considerations may improve future experiments and lead to greater insight into cardiac tissue structure, properties, and ultimately performance.

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Differential contribution of cardiac sarcomeric proteins in the myofibrillar force response to stretch

Cited by 38 publications

References 51 publications

Impact of titin strain on the cardiac slow force response

Impact of titin strain on the cardiac slow force response

Calcium sensitivity and the Frank–Starling mechanism of the heart are increased in titin N2B region-deficient mice

Cardiac Tissue Structure, Properties, and Performance: A Materials Science Perspective

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