Modeling of Cardiac Muscle Contraction Based on the Cross-Bridge Mechanism

We investigated whether changing thin filament Ca2+ sensitivity alters the rate of contraction, either during normal cross-bridge cycling or when cross-bridge cycling is increased by inorganic phosphate (Pi). We increased or decreased Ca2+ 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 1) Ca2+ sensitivity of ktr was increased by V44QTnCF27W and decreased by F20QTnCF27W compared with control TnCF27W; 2) ktr at submaximal Ca2+ activation was significantly faster for V44QTnCF27W and slower for F20QTnCF27W compared with control TnCF27W; 3) at maximum Ca2+ activation, ktr values were similar for control TnCF27W, V44QTnCF27W, and F20QTnCF27W; and 4) ktr exhibited a linear dependence on force that was indistinguishable for all TnCs. In the presence of 2.5 mM Pi, ktr was faster at all pCa values compared with the values for no added Pi for TnCF27W, V44QTnCF27W, and F20QTnCF27W. This study suggests that TnC Ca2+ binding properties modulate the rate of cardiac muscle contraction at submaximal levels of Ca2+ activation. This result has physiological relevance considering that, on a beat-to-beat basis, the heart contracts at submaximal Ca2+ activation.

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A nonlinear nonlocal transport system related to the cross-bridge mechanism of muscle contraction

Nonlinear Analysis Real World Applications ◽

10.1016/s0362-546x(99)00211-4 ◽

2000 ◽

Vol 1 (2) ◽

pp. 223-245

Author(s):

Toshitaka Matsumoto ◽

Shinnosuke Oharu ◽

Toshiyuki Yamaguchi

Keyword(s):

Muscle Contraction ◽

Transport System ◽

Cross Bridge ◽

Nonlocal Transport ◽

The Cross ◽

Cross Bridge Mechanism

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Molecular Mechanism for the Regulation of Cardiac Muscle Contraction by Troponin

Biophysical Journal ◽

10.1016/j.bpj.2013.11.248 ◽

2014 ◽

Vol 106 (2) ◽

pp. 32a

Author(s):

Ivanka Sevrieva ◽

Andrea Knowles ◽

Yin-Biao Sun

Keyword(s):

Muscle Contraction ◽

Cardiac Muscle ◽

Molecular Mechanism ◽

Cardiac Muscle Contraction

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The Frank-Starling mechanism is not mediated by changes in rate of cross-bridge detachment

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.273.5.h2428 ◽

1997 ◽

Vol 273 (5) ◽

pp. H2428-H2435 ◽

Cited By ~ 17

Author(s):

Thomas Wannenburg ◽

Paul M. L. Janssen ◽

Dongsheng Fan ◽

Pieter P. De Tombe

Keyword(s):

Cardiac Muscle ◽

Maximum Rate ◽

Sarcomere Length ◽

Myosin Head ◽

Isometric Force ◽

Force Development ◽

Cross Bridge ◽

Average Slope ◽

The Cross ◽

Kinetics Of

We tested the hypothesis that the Frank-Starling relationship is mediated by changes in the rate of cross-bridge detachment in cardiac muscle. We simultaneously measured isometric force development and the rate of ATP consumption at various levels of Ca2+ activation in skinned rat cardiac trabecular muscles at three sarcomere lengths (2.0, 2.1, and 2.2 μm). The maximum rate of ATP consumption was 1.5 nmol ⋅ s−1 ⋅ μl fiber vol−1, which represents an estimated adenosinetriphosphatase (ATPase) rate of ∼10 s−1 per myosin head at 24°C. The rate of ATP consumption was tightly and linearly coupled to the level of isometric force development, and changes in sarcomere length had no effect on the slope of the force-ATPase relationships. The average slope of the force-ATPase relationships was 15.5 pmol ⋅ mN−1 ⋅ mm−1. These results suggest that the mechanisms that underlie the Frank-Starling relationship in cardiac muscle do not involve changes in the kinetics of the apparent detachment step in the cross-bridge cycle.

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Calcium is released from the junctional sarcoplasmic reticulum during cardiac muscle contraction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.260.3.h989 ◽

1991 ◽

Vol 260 (3) ◽

pp. H989-H997 ◽

Cited By ~ 3

Author(s):

C. S. Moravec ◽

M. Bond

Keyword(s):

Sarcoplasmic Reticulum ◽

Muscle Contraction ◽

Cardiac Muscle ◽

Electron Probe Microanalysis ◽

Electron Probe ◽

Storage Site ◽

Papillary Muscles ◽

Cardiac Muscle Contraction ◽

Intracellular Storage ◽

Junctional Sarcoplasmic Reticulum

We have used electron-probe microanalysis (EPMA) to address the question of Ca2+ release by junctional sarcoplasmic reticulum (JSR) as well as Ca2+ regulation by mitochondria (MT) during cardiac muscle contraction. Hamster papillary muscles were rapidly frozen during relaxation or at the peak rate of tension rise (+dT/dt). Total Ca2+ content was measured by EPMA in the JSR, within a MT, over the A band, and in the whole cell, in nine cells per animal (five animals per group). JSR Ca2+ content was found to be significantly lower in muscles frozen at the peak of contraction [7.3 +/- 1.3 (mean +/- SE) mmol Ca2+/kg dry wt] than in those frozen during relaxation (12.5 +/- 1.9 mmol Ca2+/kg dry wt; P less than 0.01), suggesting that Ca2+ is released from this storage site during cardiac muscle contraction. In contrast, MT Ca2+ content did not change significantly during contraction (0.4 +/- 0.1 mmol/kg dry wt) compared with relaxation (0.1 +/- 0.2 mmol/kg dry wt). A third group of muscles was frozen during relaxation after pretreatment with 10(-7) M ryanodine. Ca2+ content of the JSR was significantly decreased (P less than 0.01) in this group of muscles, (6.4 +/- 1.8 mmol/kg dry wt) compared with those frozen during relaxation in the absence of the drug. This suggests that the intracellular storage site with a decreased Ca2+ content in muscles frozen at the peak of contraction is the ryanodine-releasable store. These results provide the first direct measurement of the Ca2+ content of both JSR and MT during a normal cardiac muscle contraction and demonstrate that Ca2+ is released from the JSR during muscle contraction.

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