title: Role of the JP45-Calsequestrin Complex on Calcium Entry in Slow Twitch Skeletal Muscles.
abstract: We exploited a variety of mouse models to assess the roles of JP45-CASQ1 (CASQ, calsequestrin) and JP45-CASQ2 on calcium entry in slow twitch muscles. In flexor digitorum brevis (FDB) fibers isolated from JP45-CASQ1-CASQ2 triple KO mice, calcium transients induced by tetanic stimulation rely on calcium entry via La(3+)- and nifedipine-sensitive calcium channels. The comparison of excitation-coupled calcium entry (ECCE) between FDB fibers from WT, JP45KO, CASQ1KO, CASQ2KO, JP45-CASQ1 double KO, JP45-CASQ2 double KO, and JP45-CASQ1-CASQ2 triple KO shows that ECCE enhancement requires ablation of both CASQs and JP45. Calcium entry activated by ablation of both JP45-CASQ1 and JP45-CASQ2 complexes supports tetanic force development in slow twitch soleus muscles. In addition, we show that CASQs interact with JP45 at Ca(2+) concentrations similar to those present in the lumen of the sarcoplasmic reticulum at rest, whereas Ca(2+) concentrations similar to those present in the SR lumen after depolarization-induced calcium release cause the dissociation of JP45 from CASQs. Our results show that the complex JP45-CASQs is a negative regulator of ECCE and that tetanic force development in slow twitch muscles is supported by the dynamic interaction between JP45 and CASQs.
authors.affiliation: Department of Life Science and Biotechnology, University of Ferrara, Via Borsari 46, 44100, Ferrara, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mosca
authors.affiliation: From the Departments of Anaesthesia and Biomedicine, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Eckhardt
authors.affiliation: Department of Life Science and Biotechnology, University of Ferrara, Via Borsari 46, 44100, Ferrara, Italy.
authors.forename: Leda
authors.initials: L
authors.lastname: Bergamelli
authors.affiliation: Department of Life Science and Biotechnology, University of Ferrara, Via Borsari 46, 44100, Ferrara, Italy From the Departments of Anaesthesia and Biomedicine, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland.
authors.forename: Susan
authors.initials: S
authors.lastname: Treves
authors.affiliation: Molecular Cardiology Laboratories Fondazione Salvatore Maugeri, Via Maugeri 10/10°, 27100, Pavia Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Bongianino
authors.affiliation: Molecular Cardiology Laboratories Fondazione Salvatore Maugeri, Via Maugeri 10/10°, 27100, Pavia Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: De Negri
authors.affiliation: Molecular Cardiology Laboratories Fondazione Salvatore Maugeri, Via Maugeri 10/10°, 27100, Pavia Italy, Department of Molecular Medicine, University of Pavia, Pavia Italy, and.
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Priori
authors.affiliation: Center for Research on Ageing and Translational Medicine and DNICS (Department of Neuroscience, Imaging, and Clinical Sciences), University G. d'Annunzio, 66100 Chieti, Italy.
authors.forename: Feliciano
authors.initials: F
authors.lastname: Protasi
authors.affiliation: From the Departments of Anaesthesia and Biomedicine, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland, Department of Life Science and Biotechnology, University of Ferrara, Via Borsari 46, 44100, Ferrara, Italy zor@unife.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zorzato
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002155:Calsequestrin / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009119:Muscle Contraction; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000235:genetics / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D002155:Calsequestrin; C503130:Casq1 protein, mouse; C485996:JP-45 protein, mouse; D008565:Membrane Proteins; C514388:casq2 protein, mouse; D002118:Calcium
keywords: calcium-binding protein; excitation-contraction coupling (E-C coupling); gene knockout; muscle physiology; sarcoplasmic reticulum (SR)