Neuromuscular synapse electrophysiology in myasthenia gravis animal models

• Published in: Annals of the New York Academy of Sciences Vol. 1412; no. 1; pp. 146 - 153
• Main Authors: Plomp, Jaap J., Huijbers, Maartje G.M., Verschuuren, Jan J.G.M.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2018
• Subjects: acetylcholine receptor; Acetylcholine receptors; Animal models; Autoantibodies; Electrophysiology; endplate potential; Microelectrodes; Muscle contraction; Muscles; Myasthenia gravis; neuromuscular junction; Neuromuscular junctions; Neuromuscular transmission; Proteins; Receptors; Safety factors; Skeletal muscle; synaptic homeostasis; myasthenia gravis; acetylcholine receptor; electrophysiology; synaptic homeostasis; neuromuscular junction; endplate potential
• ISSN: 0077-8923; 1749-6632; 1749-6632
• DOI: 10.1111/nyas.13507

The neuromuscular junction (NMJ) forms the synaptic connection between a motor neuron and a skeletal muscle fiber. In order to achieve a sustained muscle contraction, this synapse has to reliably transmit motor neuronal action potentials onto the muscle fiber. To guarantee successful transmission even during intense activation of the NMJ, a safety factor of neuromuscular transmission exists. In the neuromuscular disorder myasthenia gravis (MG), autoantibodies are directed against acetylcholine receptors or, in the rarer variants, against other postsynaptic NMJ proteins. This causes loss of functional acetylcholine receptors, which compromises the safety factor of neuromuscular transmission, leading to the typical fatigable muscle weakness of MG. With intracellular microelectrode measurement of (miniature) endplate potentials at NMJs in ex vivo nerve–muscle preparations from MG animal models, these functional synaptic defects have been determined in much detail. Here, we describe the electrophysiological events at the normal NMJ and the pathoelectrophysiology at NMJs of animal models for MG.