Comprehensive Simulation of Ca2+ Transients in the Continuum of Mouse Skeletal Muscle Fiber Types

Mag-Fluo-4 has revealed differences in the kinetics of the Ca2+ transients of mammalian fiber types (I, IIA, IIX, and IIB). We simulated the changes in [Ca2+] through the sarcomere of these four fiber types, considering classical (troponin –Tn–, parvalbu...

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Autores principales:	Oscar A. Rincón, Andrés F. Milán, Juan C. Calderón, Marco A. Giraldo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ECC Ca<sup>2+</sup> dyes mathematical simulation muscle cells tetanus Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/65f3e5ed2f304c34ba25959b23c063bd
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spelling	oai:doaj.org-article:65f3e5ed2f304c34ba25959b23c063bd2021-11-25T17:56:00ZComprehensive Simulation of Ca<sup>2+</sup> Transients in the Continuum of Mouse Skeletal Muscle Fiber Types10.3390/ijms2222123781422-00671661-6596https://doaj.org/article/65f3e5ed2f304c34ba25959b23c063bd2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12378https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Mag-Fluo-4 has revealed differences in the kinetics of the Ca<sup>2+</sup> transients of mammalian fiber types (I, IIA, IIX, and IIB). We simulated the changes in [Ca<sup>2+</sup>] through the sarcomere of these four fiber types, considering classical (troponin –Tn–, parvalbumin –Pv–, adenosine triphosphate –ATP–, sarcoplasmic reticulum Ca<sup>2+</sup> pump –SERCA–, and dye) and new (mitochondria –MITO–, Na<sup>+</sup>/Ca<sup>2+</sup> exchanger –NCX–, and store-operated calcium entry –SOCE–) Ca<sup>2+</sup> binding sites, during single and tetanic stimulation. We found that during a single twitch, the sarcoplasmic peak [Ca<sup>2+</sup>] for fibers type IIB and IIX was around 16 µM, and for fibers type I and IIA reached 10–13 µM. The release rate in fibers type I, IIA, IIX, and IIB was 64.8, 153.6, 238.8, and 244.5 µM ms<sup>−1</sup>, respectively. Both the pattern of change and the peak concentrations of the Ca<sup>2+</sup>-bound species in the sarcoplasm (Tn, PV, ATP, and dye), the sarcolemma (NCX, SOCE), and the SR (SERCA) showed the order IIB ≥ IIX > IIA > I. The capacity of the NCX was 2.5, 1.3, 0.9, and 0.8% of the capacity of SERCA, for fibers type I, IIA, IIX, and IIB, respectively. MITO peak [Ca<sup>2+</sup>] ranged from 0.93 to 0.23 µM, in fibers type I and IIB, respectively, while intermediate values were obtained in fibers IIA and IIX. The latter numbers doubled during tetanic stimulation. In conclusion, we presented a comprehensive mathematical model of the excitation–contraction coupling that integrated most classical and novel Ca<sup>2+</sup> handling mechanisms, overcoming the limitations of the fast- vs. slow-fibers dichotomy and the use of slow dyes.Oscar A. RincónAndrés F. MilánJuan C. CalderónMarco A. GiraldoMDPI AGarticleECCCa<sup>2+</sup> dyesmathematical simulationmuscle cellstetanusBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12378, p 12378 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ECC Ca<sup>2+</sup> dyes mathematical simulation muscle cells tetanus Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	ECC Ca<sup>2+</sup> dyes mathematical simulation muscle cells tetanus Biology (General) QH301-705.5 Chemistry QD1-999 Oscar A. Rincón Andrés F. Milán Juan C. Calderón Marco A. Giraldo Comprehensive Simulation of Ca<sup>2+</sup> Transients in the Continuum of Mouse Skeletal Muscle Fiber Types
description	Mag-Fluo-4 has revealed differences in the kinetics of the Ca<sup>2+</sup> transients of mammalian fiber types (I, IIA, IIX, and IIB). We simulated the changes in [Ca<sup>2+</sup>] through the sarcomere of these four fiber types, considering classical (troponin –Tn–, parvalbumin –Pv–, adenosine triphosphate –ATP–, sarcoplasmic reticulum Ca<sup>2+</sup> pump –SERCA–, and dye) and new (mitochondria –MITO–, Na<sup>+</sup>/Ca<sup>2+</sup> exchanger –NCX–, and store-operated calcium entry –SOCE–) Ca<sup>2+</sup> binding sites, during single and tetanic stimulation. We found that during a single twitch, the sarcoplasmic peak [Ca<sup>2+</sup>] for fibers type IIB and IIX was around 16 µM, and for fibers type I and IIA reached 10–13 µM. The release rate in fibers type I, IIA, IIX, and IIB was 64.8, 153.6, 238.8, and 244.5 µM ms<sup>−1</sup>, respectively. Both the pattern of change and the peak concentrations of the Ca<sup>2+</sup>-bound species in the sarcoplasm (Tn, PV, ATP, and dye), the sarcolemma (NCX, SOCE), and the SR (SERCA) showed the order IIB ≥ IIX > IIA > I. The capacity of the NCX was 2.5, 1.3, 0.9, and 0.8% of the capacity of SERCA, for fibers type I, IIA, IIX, and IIB, respectively. MITO peak [Ca<sup>2+</sup>] ranged from 0.93 to 0.23 µM, in fibers type I and IIB, respectively, while intermediate values were obtained in fibers IIA and IIX. The latter numbers doubled during tetanic stimulation. In conclusion, we presented a comprehensive mathematical model of the excitation–contraction coupling that integrated most classical and novel Ca<sup>2+</sup> handling mechanisms, overcoming the limitations of the fast- vs. slow-fibers dichotomy and the use of slow dyes.
format	article
author	Oscar A. Rincón Andrés F. Milán Juan C. Calderón Marco A. Giraldo
author_facet	Oscar A. Rincón Andrés F. Milán Juan C. Calderón Marco A. Giraldo
author_sort	Oscar A. Rincón
title	Comprehensive Simulation of Ca<sup>2+</sup> Transients in the Continuum of Mouse Skeletal Muscle Fiber Types
title_short	Comprehensive Simulation of Ca<sup>2+</sup> Transients in the Continuum of Mouse Skeletal Muscle Fiber Types
title_full	Comprehensive Simulation of Ca<sup>2+</sup> Transients in the Continuum of Mouse Skeletal Muscle Fiber Types
title_fullStr	Comprehensive Simulation of Ca<sup>2+</sup> Transients in the Continuum of Mouse Skeletal Muscle Fiber Types
title_full_unstemmed	Comprehensive Simulation of Ca<sup>2+</sup> Transients in the Continuum of Mouse Skeletal Muscle Fiber Types
title_sort	comprehensive simulation of ca<sup>2+</sup> transients in the continuum of mouse skeletal muscle fiber types
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/65f3e5ed2f304c34ba25959b23c063bd
work_keys_str_mv	AT oscararincon comprehensivesimulationofcasup2suptransientsinthecontinuumofmouseskeletalmusclefibertypes AT andresfmilan comprehensivesimulationofcasup2suptransientsinthecontinuumofmouseskeletalmusclefibertypes AT juanccalderon comprehensivesimulationofcasup2suptransientsinthecontinuumofmouseskeletalmusclefibertypes AT marcoagiraldo comprehensivesimulationofcasup2suptransientsinthecontinuumofmouseskeletalmusclefibertypes
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Comprehensive Simulation of Ca<sup>2+</sup> Transients in the Continuum of Mouse Skeletal Muscle Fiber Types

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