Data from: Alcohol reduces muscle fatigue through atomistic interactions with nicotinic receptors

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.

酒精摄入会影响诸多器官与组织，其中包括骨骼肌。然而，乙醇对骨骼肌发挥作用的分子机制目前仍未阐明。本研究借助分子动力学模拟与单通道记录技术，发现乙醇可与神经肌肉烟碱型乙酰胆碱受体（neuromuscular nicotinic acetylcholine receptor, nAChR）细胞外区域内的带负电荷氨基酸结合，进而改变受体的整体构象，并降低其单通道电流振幅。对该带负电荷氨基酸实施电荷反转突变，可完全阻断乙醇与nAChR的相互作用。此外，通过搭载该电荷反转突变的转基因动物模型，离体肌肉力量检测结果显示：乙醇可缓解野生型动物的肌肉疲劳，但对纯合子αE83K突变体动物无此效应。与之相符的是，乙醇给药后的运动协调能力体内研究表明，与纯合子突变体动物相比，野生型动物的运动协调能力提升约两倍。综上，从分子层面到动物层面的一系列一致性研究结果提示，乙醇可通过与神经肌肉nAChRs结合，缓解骨骼肌疲劳。