Altered myoplasmic Ca2 handling in rat fast-twitch skeletal muscle fibres during disuse atrophy

作者：Weiss Norbert; Andrianjafiniony Tina; Dupre Aucouturier Sylvie; Pouvreau Sandrine; Desplanches Dominique; Jacquemond Vincent^*

来源：Pflugers Archiv-European Journal of Physiology, 2010, 459(4): 631-644.

DOI：10.1007/s00424-009-0764-x

• Sarcoplasmic reticulum Ca2 release
• Myoplasmic calcium removal
• Skeletal muscle
• Skeletal muscle fibre
• Excitation-contraction coupling
• Calcium release
• Calcium removal
• Ryanodine receptor
• Calcium ATPase
• Calcium buffer
• Voltage clamp
• Muscle plasticity
• Rat

Calcium-dependent signalling pathways are believed to play an important role in skeletal muscle atrophy, but whether intracellular Ca2+ 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 Ca2+ current was found similar in fibres from control and HU animals. In fibres loaded with the Ca2+ dye indo-1, the value for the rate of [Ca2+] 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 Ca2+ removal. However, there was no change in the relative amount of parvalbumin, and type 1 sarco-endoplasmic reticulum Ca2+-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 [Ca2+] transients accompanied by an increase in resting [Ca2+] and a reduction of the peak amplitude of the transients. Overall results provide the first functional evidence for severely altered intracellular Ca2+ removal capabilities in atrophied fast-type muscle fibres and highlight the possible contribution of reduced mitochondrial polarisation.

• 出版日期2010-3