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- W2912797537 abstract "An isolated cardiomyocyte has the ability to adapt its force of contraction to counter an increase in mechanical load. We hypothesize that this adaptive response involves a number of cellular subsystems that regulate calcium. However, we do not know a priori which subsystems are modulated. This work describes our approach to identifying cellular subsystems that are part of the functional connectome of the mechanically loaded cardiomyocyte. We use a mathematical model to simulate the effects of a mechanical load on a cardiomyocyte. Our model implements a feedback-control system that involves the cardiomyocyte's contractile and calcium systems. Since the mechanically-activated messenger can affect many cellular subsystems in the calcium system, we consider the possibility of modulations that either inhibit or promote the activity of many subsystems. The subsystems we choose to consider are the L-type Ca2+ current (LTCC), Na+-Ca2+ exchanger (NCX), ryanodine receptors (RyRs), and SR pump subsystems. This multi-subsystem approach is complemented with a filtering method that takes advantage of multi-dimensional aspect of the experimental data. This multi-subsystem/multi-dimensional data approach allows us to cover many possible pathways of the mechanism involved in the cell's response to mechanical load while retaining only the modulations that conform to the experimental results. We found that there is no unique solution that conforms to all available experimental data. Instead, it is possible for the mechanically-activated messenger to modulate all considered subsystems in different ways. This suggests that there exists multiple “good enough” modulations capable of affecting subsystems related to the efflux and influx of calcium in a manner that qualitatively matches the experimental data. In a separate abstract, we discuss the connections between subsystems that enable the myocyte to respond to mechanical load." @default.
- W2912797537 created "2019-02-21" @default.
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- W2912797537 date "2019-02-01" @default.
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- W2912797537 title "Functional Connectome of the Mechanically Loaded Cardiomyocyte I: Identifying Involved Subsystems" @default.
- W2912797537 doi "https://doi.org/10.1016/j.bpj.2018.11.1300" @default.
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