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High-frequency fatigue of skeletal muscle: role of extracellular Ca2+

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Abstract

The present study evaluated whether Ca2+ entry operates during fatigue of skeletal muscle. The involvement of different skeletal muscle membrane calcium channels and of the Na+/Ca2+ exchanger (NCX) has been examined. The decline of force was analysed in vitro in mouse soleus and EDL muscles submitted to 60 and 110 Hz continuous stimulation, respectively. Stimulation with this high-frequency fatigue (HFF) protocol, in Ca2+-free conditions, caused in soleus muscle a dramatic increase of fatigue, while in the presence of high Ca2+ fatigue was reduced. In EDL muscle, HFF was not affected by external Ca2+ levels either way, suggesting that external Ca2+ plays a general protective role only in soleus. Calciseptine, a specific antagonist of the cardiac isoform (α1C) of the dihydropyridine receptor, gadolinium, a blocker of both stretch-activated and store-operated Ca2+ channels, as well as inhibitors of P2X receptors did not affect the development of HFF. Conversely, the Ca2+ ionophore A23187 increased the protective action of extracellular Ca2+. KB-R7943, a selective inhibitor of the reverse mode of NCX, produced an effect similar to that of Ca2+-free solution. These results indicate that a transmembrane Ca2+ influx, mainly through NCX, may play a protective role during HFF development in soleus muscle.

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Acknowledgments

This work was supported by Italian Prin 2003 and Association Française contre les Miopathies to Danieli-Betto, NIH HL63903 (Philip T. Palade and subcontract Daniela Danieli-Betto), Italian Space Agency and institutional funds from the C.N.R of Italy (Romeo Betto).

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Correspondence to Daniela Danieli-Betto.

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Germinario, E., Esposito, A., Midrio, M. et al. High-frequency fatigue of skeletal muscle: role of extracellular Ca2+ . Eur J Appl Physiol 104, 445–453 (2008). https://doi.org/10.1007/s00421-008-0796-5

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