Divet A, Lompre AM, Huchet-Cadiou C.Effect of
cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum
Ca-ATPase, on skeletal muscles from normal and mdx mice.
Acta Physiol Scand. 2005 Jul;184(3):173-86.
CNRS UMR 6204, Faculté des Sciences et des Techniques,
Université de Nantes, Nantes, Cedex 03, France.
AIM: In this study, we investigated Ca2+ loading by the
sarcoplasmic reticulum in skeletal muscle from mdx mice, an
animal model of human Duchenne's muscular dystrophy, at two
stages of development: 4 and 11 weeks. METHOD: Experiments were
conducted on fast- (extensor digitorum longus, EDL) and slow-
(soleus) twitch muscles expressing different isoforms of
Ca2+-ATPase, which is responsible for the uptake of Ca2+ by the
sarcoplasmic reticulum. RESULTS: In sarcoplasmic reticulum
vesicles, the ATP-dependent activity and sensitivity to
cyclopiazonic acid (CPA), an inhibitor of the sarcoplasmic
reticulum Ca2+-ATPase, were similar in mdx and normal EDL
muscle. Furthermore, in chemically-skinned fibres from both
normal and mdx muscles, the presence of CPA induced a decrease
in Ca2+ uptake by the sarcoplasmic reticulum. However, the
sensitivity to CPA was lower in mdx EDL muscle than in normal
muscle. In addition, in EDL muscle from 4-week-old mdx mice, the
expression of the slow Ca2+-pump isoform (SERCA2a) was
significantly increased, without any accompanying change in slow
myosin expression. In contrast, the expression and function of
the Ca2+-ATPase in mdx soleus muscles at 4- and 11-weeks of
development did not differ from those in age-matched controls.
CONCLUSION: These findings show that in dystrophic muscle, where
the Ca2+ homeostasis was perturbed, the Ca2+ handling by the
sarcoplasmic reticulum was altered in fast-twitch muscle, and
this was associated with the expression of the slow isoform of
SERCA. In these muscles, reduced Ca2+ uptake could then
contribute to an elevated concentration of Ca2+ in the cytosol,
and also to Ca2+ depletion of the sarcoplasmic reticulum.
PMID: 15954985
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