Acetylcholine release in diaphragm of rats with chronic experimental autoimmune myasthenia gravis

Authors

  • Dr. John J. Kelly Jr,

    MD, Corresponding author
    1. Department of Neurology and the Neuromuscular Physiology Research Laboratory, Mayo Clinic and Mayo Foundation, Rochester, MN
    2. The Salk Institute for Biological Studies, San Diego, CA
    • Department of Neurology, Mayo Clinic, Rochester, MN 55901
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  • Edward H. Lambert PhD,

    MD
    1. Department of Neurology and the Neuromuscular Physiology Research Laboratory, Mayo Clinic and Mayo Foundation, Rochester, MN
    2. The Salk Institute for Biological Studies, San Diego, CA
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  • Vanda A. Lennon PhD

    MD
    1. Department of Neurology and the Neuromuscular Physiology Research Laboratory, Mayo Clinic and Mayo Foundation, Rochester, MN
    2. The Salk Institute for Biological Studies, San Diego, CA
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Abstract

Recent evidence indicates that in chronic experimental autoimmune myasthenia gravis (EAMG) and in human myasthenia gravis, the defect of neuromuscular transmission results from immune-mediated destruction of postsynaptic membrane at the neuromuscular junction, with a reduction in the density of acetylcholine (ACh) receptors and decreased sensitivity to ACh released by nerve impulses. In the present study, the amount of ACh released by nerve impulse in rats with chronic EAMG and control rats of the same age, weight, and sex was compared. Phrenic nerve–hemidiaphragm preparations were stimulated in vitro, and the amount of ACh released was meansured by bioassay. Despite a marked reduction in the amplitude of miniature end-plate potentials in chronic EAMG, ACh output at rest and during stimulation was not different from that of control rats. These data support the concept that the defect of neuromuscular transmission is due to a reduction of postsynaptic sensitivity to ACh.

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