Reorganized stores and impaired calcium handling in skeletal muscle of mice lacking calsequestrin-1

Cecilia Paolini, Marco Quarta, Alessandra Nori, Simona Boncompagni, Marta Canato, Pompeo Volpe, Paul D. Allen, Carlo Reggiani, Feliciano Protasi

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Calsequestrin (CS), the major Ca2+-binding protein in the sarcoplasmic reticulum (SR), is thought to play a dual role in excitation-contraction coupling: buffering free Ca2+ increasing SR capacity, and modulating the activity of the Ca2+ release channels (RyRs). In this study, we generated and characterized the first murine model lacking the skeletal CS isoform (CS1). CS1-null mice are viable and fertile, even though skeletal muscles appear slightly atrophic compared to the control mice. No compensatory increase of the cardiac isoform CS2 is detectable in any type of skeletal muscle. CS1-null muscle fibres are characterized by structural and functional changes, which are much more evident in fast-twitch muscles (EDL) in which most fibres express only CS1, than in slow-twitch muscles (soleus), where CS2 is expressed in about 50% of the fibres. In isolated EDL muscle, force development is preserved, but characterized by prolonged time-to-peak and half-relaxation time, probably related to impaired calcium release from and re-uptake by the SR. Ca2+-imaging studies show that the amount of Ca2+ released from the SR and the amplitude of the Ca2+ transient are significantly reduced. The lack of CS1 also causes significant ultrastructural changes, which include: (i) striking proliferation of SR junctional domains; (ii) increased density of Ca2+-release channels (confirmed also by 3 H-ryanodine binding); (iii) decreased SR terminal cisternae volume; (iv) higher density of mitochondria. Taken together these results demonstrate that CS1 is essential for the normal development of the SR and its calcium release units and for the storage and release of appropriate amounts of SR Ca2+.

Original languageEnglish (US)
Pages (from-to)767-784
Number of pages18
JournalJournal of Physiology
Volume583
Issue number2
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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    Paolini, C., Quarta, M., Nori, A., Boncompagni, S., Canato, M., Volpe, P., Allen, P. D., Reggiani, C., & Protasi, F. (2007). Reorganized stores and impaired calcium handling in skeletal muscle of mice lacking calsequestrin-1. Journal of Physiology, 583(2), 767-784. https://doi.org/10.1113/jphysiol.2007.138024