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Increase in phospholamban content in mouse skeletal muscle after denervation

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Abstract

It is well-known that denervation of motor nerves induces atrophy and decreases contractile force of the skeletal muscle. However, it is not completely understood how denervation alters calcium handling in the skeletal muscle. We investigated the effect of denervation on the expression and function of proteins involved in calcium handling. Two weeks after denervation of the right sciatic nerve in mice, we observed a significant decrease in mass and cross-sectional area of the ipsilateral tibialis anterior (TA) and flexor digitorum brevis (FDB) muscles. Also, we observed a significant decrease in the specific tetanus contractile force in the ipsilateral TA muscle. Calcium imaging of the ipsilateral FDB showed that the peak twitch and tetanus calcium concentrations were significantly decreased due to a decrease in calcium content of the sarcoplasmic reticulum (SR). Denervation reduced the maximum rate of sarcoplasmic/endoplasmic calcium ATPase (SERCA) activity. Interestingly, the amount of phospholamban (PLN), but not its transcripts, was increased in the ipsilateral vs. contralateral side after denervation, suggesting that denervation impairs constitutive regulation of PLN. Immunohistochemical analysis revealed increased PLN in all major fiber types in TA with IIx fibers showing a threefold higher expression than the contralateral side. These results suggest that the abnormal increase in PLN in the ipsilateral fast-twitch fibers may be involved in decreased SERCA activity, SR calcium content, peak calcium transients, and contractile forces of denervated muscles.

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Acknowledgements

We are grateful to Ms. Reiko Sakai for her secretarial assistance. This work was supported by Grants-in-aid for Scientific Research 25670641 (to HK) and 16K20046 (to MK) from the Ministry of Education, Culture, Sport, Science and Technology of Japan (MEXT) and a grant (to TN) from Shinshu Public Utility Foundation for Promotion of Medical Sciences,  and by a research grant 41290769 from MSDKK (Tokyo, Japan) to MY.

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Correspondence to Tsutomu Nakada or Mitsuhiko Yamada.

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Komatsu, M., Nakada, T., Kawagishi, H. et al. Increase in phospholamban content in mouse skeletal muscle after denervation. J Muscle Res Cell Motil 39, 163–173 (2018). https://doi.org/10.1007/s10974-019-09504-2

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  • DOI: https://doi.org/10.1007/s10974-019-09504-2

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