Alcohol reduces muscle fatigue through atomistic interactions with nicotinic receptors

Hamid R. Noori, Christian Mücksch, Valentina Vengeliene, Kai Schönig, Tatiane T. Takahashi, Nuriya Mukhtasimova, Maryam Bagher Oskouei, Matias Mosqueira, Dusan Bartsch, Rainer Fink, Herbert M. Urbassek, Rainer Spanagel, Steven M Sine

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number159
JournalCommunications Biology
Volume1
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

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  • Cite this

    Noori, H. R., Mücksch, C., Vengeliene, V., Schönig, K., Takahashi, T. T., Mukhtasimova, N., Bagher Oskouei, M., Mosqueira, M., Bartsch, D., Fink, R., Urbassek, H. M., Spanagel, R., & Sine, S. M. (2018). Alcohol reduces muscle fatigue through atomistic interactions with nicotinic receptors. Communications Biology, 1(1), [159]. https://doi.org/10.1038/s42003-018-0157-9