Altered myoplasmic Ca(2+) handling in rat fast-twitch skeletal muscle fibres during disuse atrophy.
Calcium-dependent signalling pathways are believed to play an important role in skeletal muscle atrophy, but whether intracellular Ca(2+) homeostasis is affected in that situation remains obscure. We show here that there is a 20% atrophy of the fast-type flexor digitorum brevis (FDB) muscle in rats hind limb unloaded (HU) for 2 weeks, with no change in fibre type distribution. In voltage-clamp experiments, the amplitude of the slow Ca(2+) current was found similar in fibres from control and HU animals. In fibres loaded with the Ca(2+) dye indo-1, the value for the rate of [Ca(2+)] decay after the end of 5-100-ms-long voltage-clamp depolarisations from -80 to +10 mV was found to be 30-50% lower in fibres from HU animals. This effect was consistent with a reduced contribution of both saturable and non-saturable components of myoplasmic Ca(2+) removal. However, there was no change in the relative amount of parvalbumin, and type 1 sarco-endoplasmic reticulum Ca(2+)-ATPase was increased by a factor of three in the atrophied muscles. Confocal imaging of mitochondrial membrane potential showed that atrophied FDB fibres had significantly depolarized mitochondria as compared to control fibres. Depolarization of mitochondria in control fibres with carbonyl cyanide-p-trifluoromethoxyphenylhydrazone induced a slowing of the decay of [Ca(2+)] transients accompanied by an increase in resting [Ca(2+)] and a reduction of the peak amplitude of the transients. Overall results provide the first functional evidence for severely altered intracellular Ca(2+) removal capabilities in atrophied fast-type muscle fibres and highlight the possible contribution of reduced mitochondrial polarisation.
Weiss
Norbert
N
Physiologie Intégrative Cellulaire et Moléculaire, Université Lyon 1, UMR CNRS 5123, Bât. Raphaël Dubois, 43 boulevard du 11 novembre 1918, 69622, Villeurbanne, France.
Andrianjafiniony
Tina
T
Dupré-Aucouturier
Sylvie
S
Pouvreau
Sandrine
S
Desplanches
Dominique
D
Jacquemond
Vincent
V
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D019417:Hindlimb Suspension; D007211:Indoles / Q000378:metabolism; D007476:Ionophores / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D020966:Muscular Disorders, Atrophic / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
D005456:Fluorescent Dyes; D007211:Indoles; D007476:Ionophores; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; C048960:indo-1; D002118:Calcium