Alteration of Sarcoplasmic Reticulum Ca2+ Release in Skeletal Muscle from Calpain 3-Deficient Mice

Mutations of Ca2+-activated proteases (calpains) cause muscular dystrophies. Nevertheless, the specific role of calpains in Ca2+ signalling during the onset of dystrophies remains unclear. We investigated Ca2+ handling in skeletal cells from calpain 3-deficient mice. [Ca2+]i responses to caffeine, a...

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Main Authors: Govindan Dayanithi, Isabelle Richard, Cédric Viero, Elsa Mazuc, Sylvie Mallie, Jean Valmier, Nathalie Bourg, Muriel Herasse, Isabelle Marty, Gérard Lefranc, Paul Mangeat, Stephen Baghdiguian
Format: Article
Language:English
Published: Wiley 2009-01-01
Series:International Journal of Cell Biology
Online Access:http://dx.doi.org/10.1155/2009/340346
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author Govindan Dayanithi
Isabelle Richard
Cédric Viero
Elsa Mazuc
Sylvie Mallie
Jean Valmier
Nathalie Bourg
Muriel Herasse
Isabelle Marty
Gérard Lefranc
Paul Mangeat
Stephen Baghdiguian
author_facet Govindan Dayanithi
Isabelle Richard
Cédric Viero
Elsa Mazuc
Sylvie Mallie
Jean Valmier
Nathalie Bourg
Muriel Herasse
Isabelle Marty
Gérard Lefranc
Paul Mangeat
Stephen Baghdiguian
author_sort Govindan Dayanithi
collection DOAJ
description Mutations of Ca2+-activated proteases (calpains) cause muscular dystrophies. Nevertheless, the specific role of calpains in Ca2+ signalling during the onset of dystrophies remains unclear. We investigated Ca2+ handling in skeletal cells from calpain 3-deficient mice. [Ca2+]i responses to caffeine, a ryanodine receptor (RyR) agonist, were decreased in −/− myotubes and absent in −/− myoblasts. The −/− myotubes displayed smaller amplitudes of the Ca2+ transients induced by cyclopiazonic acid in comparison to wild type cells. Inhibition of L-type Ca2+ channels (LCC) suppressed the caffeine-induced [Ca2+]i responses in −/− myotubes. Hence, the absence of calpain 3 modifies the sarcoplasmic reticulum (SR) Ca2+ release, by a decrease of the SR content, an impairment of RyR signalling, and an increase of LCC activity. We propose that calpain 3-dependent proteolysis plays a role in activating support proteins of intracellular Ca2+ signalling at a stage of cellular differentiation which is crucial for skeletal muscle regeneration.
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institution Kabale University
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spelling doaj-art-f2d70311b13b470b8330f7dfe19dce4b2025-02-03T05:52:41ZengWileyInternational Journal of Cell Biology1687-88761687-88842009-01-01200910.1155/2009/340346340346Alteration of Sarcoplasmic Reticulum Ca2+ Release in Skeletal Muscle from Calpain 3-Deficient MiceGovindan Dayanithi0Isabelle Richard1Cédric Viero2Elsa Mazuc3Sylvie Mallie4Jean Valmier5Nathalie Bourg6Muriel Herasse7Isabelle Marty8Gérard Lefranc9Paul Mangeat10Stephen Baghdiguian11Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, European Union Centre of Excellence, Videnska 1083, 142 20 Prague 4, Czech RepublicGénéthon CNRS-UMR8587 LAMBE, 1, rue de l'Internationale, 91000 Evry, FranceDepartment of Cardiology, Wales Heart Research Institute, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UKINSERM U583, Institut des Neurosciences de Montpellier, Hôpital St Eloi, 80, rue Augustin Fliche, 34091 Montpellier, Cedex 05, FranceINSERM U583, Institut des Neurosciences de Montpellier, Hôpital St Eloi, 80, rue Augustin Fliche, 34091 Montpellier, Cedex 05, FranceINSERM U583, Institut des Neurosciences de Montpellier, Hôpital St Eloi, 80, rue Augustin Fliche, 34091 Montpellier, Cedex 05, FranceGénéthon CNRS-UMR8587 LAMBE, 1, rue de l'Internationale, 91000 Evry, FranceGénéthon CNRS-UMR8587 LAMBE, 1, rue de l'Internationale, 91000 Evry, FranceGrenoble Institut des Neurosciences, INSERM U836, Equipe Muscle et Pathologies, UJF Site santé-BP170, 38042 Grenoble Cedex 9, FranceLaboratoire d'Immunogénétique Moléculaire, UPR 1142 CNRS-Institut de Génétique Humaine, Université Montpellier 2, place Eugène Bataillon, 34095 Montpellier, Cedex 05, FranceCentre de Recherche de Biochimie Macromoléculaire, Universités Montpellier 2 & 1, 1919 Route de Mende, 34293 Montpellier, Cedex 05, FranceUMR CNRS 5554, Institut des Sciences de l'Evolution, Université Montpellier 2, place Eugène Bataillon, 34095 Montpellier, Cedex 05, FranceMutations of Ca2+-activated proteases (calpains) cause muscular dystrophies. Nevertheless, the specific role of calpains in Ca2+ signalling during the onset of dystrophies remains unclear. We investigated Ca2+ handling in skeletal cells from calpain 3-deficient mice. [Ca2+]i responses to caffeine, a ryanodine receptor (RyR) agonist, were decreased in −/− myotubes and absent in −/− myoblasts. The −/− myotubes displayed smaller amplitudes of the Ca2+ transients induced by cyclopiazonic acid in comparison to wild type cells. Inhibition of L-type Ca2+ channels (LCC) suppressed the caffeine-induced [Ca2+]i responses in −/− myotubes. Hence, the absence of calpain 3 modifies the sarcoplasmic reticulum (SR) Ca2+ release, by a decrease of the SR content, an impairment of RyR signalling, and an increase of LCC activity. We propose that calpain 3-dependent proteolysis plays a role in activating support proteins of intracellular Ca2+ signalling at a stage of cellular differentiation which is crucial for skeletal muscle regeneration.http://dx.doi.org/10.1155/2009/340346
spellingShingle Govindan Dayanithi
Isabelle Richard
Cédric Viero
Elsa Mazuc
Sylvie Mallie
Jean Valmier
Nathalie Bourg
Muriel Herasse
Isabelle Marty
Gérard Lefranc
Paul Mangeat
Stephen Baghdiguian
Alteration of Sarcoplasmic Reticulum Ca2+ Release in Skeletal Muscle from Calpain 3-Deficient Mice
International Journal of Cell Biology
title Alteration of Sarcoplasmic Reticulum Ca2+ Release in Skeletal Muscle from Calpain 3-Deficient Mice
title_full Alteration of Sarcoplasmic Reticulum Ca2+ Release in Skeletal Muscle from Calpain 3-Deficient Mice
title_fullStr Alteration of Sarcoplasmic Reticulum Ca2+ Release in Skeletal Muscle from Calpain 3-Deficient Mice
title_full_unstemmed Alteration of Sarcoplasmic Reticulum Ca2+ Release in Skeletal Muscle from Calpain 3-Deficient Mice
title_short Alteration of Sarcoplasmic Reticulum Ca2+ Release in Skeletal Muscle from Calpain 3-Deficient Mice
title_sort alteration of sarcoplasmic reticulum ca2 release in skeletal muscle from calpain 3 deficient mice
url http://dx.doi.org/10.1155/2009/340346
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