| First Author | Ottenheijm CA | Year | 2008 |
| Journal | FASEB J | Volume | 22 |
| Issue | 8 | Pages | 2912-9 |
| PubMed ID | 18434434 | Mgi Jnum | J:137953 |
| Mgi Id | MGI:3803435 | Doi | 10.1096/fj.07-104372 |
| Citation | Ottenheijm CA, et al. (2008) Sarcoplasmic reticulum calcium uptake and speed of relaxation are depressed in nebulin-free skeletal muscle. FASEB J 22(8):2912-9 |
| abstractText | Previous work suggested that altered Ca(2+) homeostasis might contribute to dysfunction of nebulin-free muscle, as gene expression analysis revealed that the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)-inhibitor sarcolipin (SLN) is up-regulated >70-fold in nebulin knockout mice, and here we tested this proposal. We investigated SLN protein expression in nebulin-free and wild-type skeletal muscle, as well as expression of other Ca(2+)-handling proteins. Ca(2+) uptake capacity was determined in isolated sarcoplasmic reticulum vesicles and in intact myofibers by measuring Ca(2+) transients. Muscle contractile performance was determined in skinned muscle activated with exogenous Ca(2+), as well as in electrically stimulated intact muscle. We found profound up-regulation of SLN protein in nebulin-free skeletal muscle, whereas expression of other Ca(2+)-handling proteins was not (calsequestrin and phospholamban) or was minimally (SERCA) affected. Speed of Ca(2+) uptake was >3-fold decreased in sarcoplasmic reticulum vesicles isolated from nebulin-free muscle as well as in nebulin-free intact myofibers. Ca(2+)-activated stress in skinned muscle and stress produced by intact nebulin-free muscle were reduced to a similar extent compared with wild type. Half-relaxation time was significantly longer in nebulin-free compared with wild-type muscle. Thus, the present study demonstrates for the first time that nebulin might also be involved in physiological Ca(2+) handling of the SR-myofibrillar system. |
