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Abstract <p>An important factor in the reliability and plasticity of neuromusculartransmission is the structural and functional organization of themotor endplate, which is a highly specialized area of the sarcolemma.The structural features of the endplate largely depend on motoractivity and change with motor dysfunction. In this study, ratswere exposed to simulated high-altitude (3000 m above sea level)hypobaric hypoxia for 3 h using a hyperbaric pressure chamber. Then,18 h after control or hypoxic conditions, rats underwent 6 h ofhindlimb suspension (HS), a model of gravitational motor unloading.Isolated soleus and diaphragm muscles were tested. Labeled α-bungarotoxinwas used to analyze the localization of nicotinic acetylcholinereceptors (nAChRs). To assess the plasma membrane properties, 22-NBD-cholesterol(NBD), a fluorescent sterol, was used. HS itself increased the fragmentationof nAChR distribution without changing the total endplate area.These changes were accompanied by an increase in the intensity ofNBD fluorescence throughout the sarcolemma, indicating destabilizationof its lipid-ordered phase. Hypoxia per se did not affect endplateintegrity and NBD fluorescence intensity. However, hypoxic pretreatmentprotected against HS-induced impairments. The relative phosphorylationlevel of AMP-activated protein kinase, a key metabolic regulator,remained unchanged. Similar effects were observed in both the soleusand diaphragm muscles. We suggest that these results may have potentialtherapeutic implications in the search for countermeasures in casesof neuromuscular disorders.</p>

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Short-Term Mild Hypoxia Maintains Endplate Integrity and Lipid Membrane Stability in Rat Skeletal Muscle under Simulated Gravitational Unloading

  • 期刊论文

  • 发表日期：

    2025年10月1日

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  • V. V. Kravtsova,
  • K. A. Sharlo,
  • A. A. Kulishenko,
  • E. A. Saburova,
  • B. S. Shenkman,
  • I. I. Krivoi

摘要

Abstract

An important factor in the reliability and plasticity of neuromusculartransmission is the structural and functional organization of themotor endplate, which is a highly specialized area of the sarcolemma.The structural features of the endplate largely depend on motoractivity and change with motor dysfunction. In this study, ratswere exposed to simulated high-altitude (3000 m above sea level)hypobaric hypoxia for 3 h using a hyperbaric pressure chamber. Then,18 h after control or hypoxic conditions, rats underwent 6 h ofhindlimb suspension (HS), a model of gravitational motor unloading.Isolated soleus and diaphragm muscles were tested. Labeled α-bungarotoxinwas used to analyze the localization of nicotinic acetylcholinereceptors (nAChRs). To assess the plasma membrane properties, 22-NBD-cholesterol(NBD), a fluorescent sterol, was used. HS itself increased the fragmentationof nAChR distribution without changing the total endplate area.These changes were accompanied by an increase in the intensity ofNBD fluorescence throughout the sarcolemma, indicating destabilizationof its lipid-ordered phase. Hypoxia per se did not affect endplateintegrity and NBD fluorescence intensity. However, hypoxic pretreatmentprotected against HS-induced impairments. The relative phosphorylationlevel of AMP-activated protein kinase, a key metabolic regulator,remained unchanged. Similar effects were observed in both the soleusand diaphragm muscles. We suggest that these results may have potentialtherapeutic implications in the search for countermeasures in casesof neuromuscular disorders.