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Role of sarcoplasmic reticulum junctional proteins in skeletal muscle strength

  • Barbara Mosca1,
  • Osvaldo Delbono2,
  • Maria Laura Messi2,
  • Leda Bergamelli1,
  • Mirko Vukcevic3,
  • Ruben Lopez1,
  • Susan Treves1, 3,
  • Miyuki Nishi4,
  • Hiroshi Takeshima4 and
  • Francesco Zorzato1, 3
BMC Anesthesiology201414(Suppl 1):A19

Published: 18 August 2014


Skeletal MuscleMuscle StrengthSarcoplasmic ReticulumChannel ActivityDihydropyridine


Skeletal muscle constitutes approximately 40% of body mass, and age-induced decrease of muscle strength impinge on daily activities and on normal social life in the elderly. Loss of muscle strength has been recognised as a debilitating and life threatening condition also in cachexia in cancer patients and in clinical conditions associated with prolonged bed rest. Skeletal muscle dihydropyridine receptors (Cav1.1) act as Ca2+ channels and voltage sensors to initiate muscle contraction by activating ryanodine receptors, the Ca2+ release channels of the sarcoplasmic reticulum. Cav1.1 activity is enhanced by a retrograde stimulatory signal delivered by the ryanodine receptor. JP45 is a membrane protein interacting with Cav1.1 and the sarcoplasmic reticulum Ca2+ storage protein calsequestrin (CASQ1).

We hypothesized that JP45 and CASQ1 form a signalling pathway which modulates Cav1.1 channel activity.

Materials and methods

We isolated flexor digitorum brevis (FDB) muscle fibres from JP45 and CASQ1 double knock-out mice (DKO) and tested whether there were differences in Ca2+ homeostasis between the different mouse lines.


Our results show that Ca2+ transients evoked by tetanic stimulation in DKO fibres, result from massive Ca2+ influx due to enhanced Cav1.1 channel activity. This enhanced activity causes an increase of muscle strength both in vitro and in vivo.


We conclude that skeletal muscle contraction is strengthened through the modulation of Cav1.1 channel activity by JP45 and CASQ1.



This work was supported by funds from Swiss Muscle foundation, A.F.M., S.N.F and Department of Biomedicine University Hospital Basel. This study was also supported by Research Grant no. GGP08153 from the Italian Telethon ONLUS Foundation to F.P. and grants from the NIH/NIA (AG13934 and AG15820) to O.D.

Authors’ Affiliations

Department of Life Sciences and Biotechnology, General Pathology section, University of Ferrara, Ferrara, Italy
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, USA
Departments of Biomedicine and Anesthesiology, Basel University Hospital, Basel, Switzerland
Department of Biological Chemistry, Graduate School of Pharmacological Sciences, Kyoto University, Tokyo, Japan


© Mosca et al; licensee BioMed Central Ltd. 2014

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