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  Alcohol reduces muscle fatigue through atomistic interactions with nicotinic receptors

Noori, H., Mücksch, C., Vengeliene, V., Schönig, K., Takahashi, T., Mukhtasimov, N., et al. (2018). Alcohol reduces muscle fatigue through atomistic interactions with nicotinic receptors. Communications Biology, 1: 159, pp. 1-11. doi:10.1038/s42003-018-0157-9.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-512F-F Version Permalink: http://hdl.handle.net/21.11116/0000-0002-9DC3-1
Genre: Journal Article

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 Creators:
Noori, HR1, 2, Author              
Mücksch, C, Author
Vengeliene, V, Author
Schönig, K, Author
Takahashi, TT, Author
Mukhtasimov, N, Author
Bagher Oskouei, M1, 2, Author              
Mosqueira, M, Author
Bartsch, D, Author
Fink, H, Author
Urbassek, HM, Author
Spanagel, R, Author
Sine, SM, Author
Affiliations:
1Research Group Neuronal Convergence, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_2528694              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497794              

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 Abstract: Alcohol consumption affects many organs and tissues, including skeletal muscle. However, the molecular mechanism of ethanol action on skeletal muscle remains unclear. Here, using molecular dynamics simulations and single channel recordings, we show that ethanol interacts with a negatively charged amino acid within an extracellular region of the neuromuscular nicotinic acetylcholine receptor (nAChR), thereby altering its global conformation and reducing the single channel current amplitude. Charge reversal of the negatively charged amino acid abolishes the nAChR-ethanol interaction. Moreover, using transgenic animals harboring the charge-reversal mutation, ex vivo measurements of muscle force production show that ethanol counters fatigue in wild type but not homozygous αE83K mutant animals. In accord, in vivo studies of motor coordination following ethanol administration reveal an approximately twofold improvement for wild type compared to homozygous mutant animals. Together, the converging results from molecular to animal studies suggest that ethanol counters muscle fatigue through its interaction with neuromuscular nAChRs.

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 Dates: 2018-10
 Publication Status: Published online
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 Identifiers: DOI: 10.1038/s42003-018-0157-9
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Title: Communications Biology
Source Genre: Journal
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Pages: - Volume / Issue: 1 Sequence Number: 159 Start / End Page: 1 - 11 Identifier: ISSN: 2399-3642