| First Author | Paolini C | Year | 2007 |
| Journal | J Physiol | Volume | 583 |
| Issue | Pt 2 | Pages | 767-84 |
| PubMed ID | 17627988 | Mgi Jnum | J:140828 |
| Mgi Id | MGI:3814667 | Doi | 10.1113/jphysiol.2007.138024 |
| Citation | Paolini C, et al. (2007) Reorganized stores and impaired calcium handling in skeletal muscle of mice lacking calsequestrin-1. J Physiol 583(Pt 2):767-84 |
| abstractText | Calsequestrin (CS), the major Ca(2+)-binding protein in the sarcoplasmic reticulum (SR), is thought to play a dual role in excitation-contraction coupling: buffering free Ca(2+) increasing SR capacity, and modulating the activity of the Ca(2+) 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. Ca(2+)-imaging studies show that the amount of Ca(2+) released from the SR and the amplitude of the Ca(2+) 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 Ca(2+)-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 Ca(2+). |
