Functionally Isolated Sarcoplasmic Reticulum in Cardiomyocytes: Experimental and Mathematical Models

The interaction among the various Ca<sup>2+</sup> transporters complicates the assessment of isolated systems in an intact cell. This article proposes the functionally isolated SR model (FISRM), a hybrid (experimental and mathematical) approach to study Ca<sup>2+</sup> cyclin...

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Bibliographic Details
Main Authors: Diogo C. Soriano, Rosana A. Bassani, José W. M. Bassani
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Bioengineering
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Online Access:https://www.mdpi.com/2306-5354/12/6/627
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Summary:The interaction among the various Ca<sup>2+</sup> transporters complicates the assessment of isolated systems in an intact cell. This article proposes the functionally isolated SR model (FISRM), a hybrid (experimental and mathematical) approach to study Ca<sup>2+</sup> cycling between the cytosol and the sarcoplasmic reticulum (SR), the main source of Ca<sup>2+</sup> for contraction in mammalian cardiomyocytes. In FISRM, the main transmembrane Ca<sup>2+</sup> transport pathways are eliminated by using a Na<sup>+</sup>, Ca<sup>2+</sup>-free extracellular medium, and SR Ca<sup>2+</sup> release is elicited by a train of brief caffeine pulses. Two compounds that exert opposite effects on the SR Ca<sup>2+</sup> uptake were characterized by this approach in isolated rat ventricular cardiomyocytes. The experimental FISRM was simulated with a simple mathematical model of Ca<sup>2+</sup> fluxes across the SR membrane, based on a previous model adapted to the present conditions. To a fair extent, the theoretical model could reproduce the experimental results, and confirm the main assumption of the experimental model: that the only relevant Ca<sup>2+</sup> fluxes occur across the SR membrane. Thus, the FISRM seems to be a valuable framework to investigate the SR Ca<sup>2+</sup> transport in intact cardiomyocytes under physiological and pathophysiological conditions, and to test therapeutic approaches targeting SR proteins.
ISSN:2306-5354