Key result
A mathematical model of mouse ventricular myocyte contraction successfully simulated the mechanisms of increased contraction force and myocyte shortening upon β1-adrenergic stimulation.
Why the study?
Chronic stimulation of the β1-adrenergic signaling system can cause cardiac hypertrophy and heart failure, requiring better understanding of the mechanisms of action of β1-adrenoceptors.
A newly developed mathematical model of mouse ventricular myocyte contraction accurately simulates β1-adrenergic regulation and drug effects, providing a computational tool for studying cardiac diseases and genetically modified models.
Answers are grounded in this paper and cite their sources.
Provides a computational tool for mouse myocyte studies; leaves open applicability to human cardiac disease models.
The β 1 -adrenergic regulation of cardiac myocyte contraction plays an important role in regulating heart function. Activation of this system leads to an increased heart rate and stronger myocyte contraction. However, chronic stimulation of the β 1 -adrenergic signaling system can lead to cardiac hypertrophy and heart failure. To understand the mechanisms of action of β 1 -adrenoceptors, a mathematical model of cardiac myocyte contraction that includes the β 1 -adrenergic system was developed and studied. The model was able to simulate major experimental protocols for measurements of steady-state force-calcium relationships, cross-bridge release rate and force development rate, force-velocity relationship, and force redevelopment rate. It also reproduced quite well frequency and isoproterenol dependencies for intracellular Ca 2+ concentration ([Ca 2+ ] i ) transients, total contraction force, and sarcomere shortening. The mathematical model suggested the mechanisms of increased contraction force and myocyte shortening on stimulation of β 1 -adrenergic receptors is due to phosphorylation of troponin I and myosin-binding protein C and increased [Ca 2+ ] i transient resulting from activation of the β 1 -adrenergic signaling system. The model was used to simulate work-loop contractions and estimate the power during the cardiac cycle as well as the effects of 4-aminopyridine and tedisamil on the myocyte contraction. The developed mathematical model can be used further for simulations of contraction of ventricular myocytes from genetically modified mice and myocytes from mice with chronic cardiac diseases. NEW & NOTEWORTHY A new mathematical model of mouse ventricular myocyte contraction that includes the β 1 -adrenergic system was developed. The model simulated major experimental protocols for myocyte contraction and predicted the effects of 4-aminopyridine and tedisamil on the myocyte contraction. The model also allowed for simulations of work-loop contractions and estimation of the power during the cardiac cycle.
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Mullins et al. (2019) studied Cardiac myocyte contraction. Mathematical model of β1-adrenergic system was evaluated. A mathematical model of mouse ventricular myocyte contraction successfully simulated the mechanisms of increased contraction force and myocyte shortening upon β1-adrenergic stimulation.
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