Title: Sarcoplasmic reticulum calcium uptake and speed of relaxation are depressed in nebulin-free skeletal muscle
Authors: Ottenheijm, Coen A. C ×
Fong, Chi
Vangheluwe, Peter
Wuytack, Frank
Babu, Gopal J
Periasamy, Muthu
Witt, Christian C
Labeit, Siegfried
Granzier, Henk #
Issue Date: Aug-2008
Publisher: The Federation of American Societies for Experimental Biology
Series Title: FASEB Journal vol:22 issue:8 pages:2912-2919
Abstract: Previous work suggested that altered Ca2+ homeostasis might contribute to dysfunction of nebulin-free muscle, as gene expression analysis revealed that the sarco(endo) plasmic reticulum Ca2+-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 Ca2+-handling proteins. Ca2+ uptake capacity was determined in isolated sarcoplasmic reticulum vesicles and in intact myofibers by measuring Ca2+ transients. Muscle contractile performance was determined in skinned muscle activated with exogenous Ca2+, 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 Ca2+-handling proteins was not (calsequestrin and phospholamban) or was minimally (SERCA) affected. Speed of Ca2(+) uptake was > 3-fold decreased in sarcoplasmic reticulum vesicles isolated from nebulin-free muscle as well as in nebulin-free intact myofibers. Ca2+-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 Ca2+ handling of the SR-myofibrillar system.
ISSN: 0892-6638
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Cellular Transport Systems
× corresponding author
# (joint) last author

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