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.
You may also like
Insulin-like hormones critical for brain plasticity
August 7, 2023Max Planck Florida Institute for Neuroscience
A Butterfly Effect
July 27, 2023Max Planck Florida Institute for Neuroscience
Poetic birdsong, precisely tuned
July 24, 2023Max Planck Institute for Biological Intelligence
Deep learning models to study sentence comprehension...
June 28, 2023Max Planck Institute for Psycholinguistics
How the brain slows down when we focus our gaze
June 28, 2023Max Planck Institute for Biological Cybernetics
Fruit fly’s complex symphony of vision
June 6, 2023Max Planck Institute for Biological Intelligence