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
Hitchhiking through the nerve cell
Getting in the Groove: Why samba makes everyone want...
Estimating the pace of change
April 26, 2022Max Planck Institute for Biological Cybernetics
Out of rhythm: Compromised precision of theta-gamma...
April 26, 2022Max Planck Institute for Human Development
Near-natural, fractal architecture promotes well-being
April 26, 2022Max Planck Institute for Biological Cybernetics
Locus coeruleus integrity is related to tau burden and...
April 26, 2022Max Planck Institute for Human Development