Neuromuscular synapse electrophysiology in myasthenia gravis animal models

Ann N Y Acad Sci. 2018 Jan;1412(1):146-153. doi: 10.1111/nyas.13507. Epub 2017 Oct 25.

Abstract

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.

Keywords: acetylcholine receptor; electrophysiology; endplate potential; myasthenia gravis; neuromuscular junction; synaptic homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholine / physiology
  • Animals
  • Calcium Signaling / physiology
  • Electrophysiological Phenomena
  • Humans
  • In Vitro Techniques
  • LDL-Receptor Related Proteins
  • Mice
  • Miniature Postsynaptic Potentials / physiology
  • Myasthenia Gravis, Autoimmune, Experimental / physiopathology*
  • Neuromuscular Junction / physiopathology*
  • Receptor Protein-Tyrosine Kinases / physiology
  • Receptors, Cholinergic / physiology
  • Receptors, LDL / physiology
  • Synapses / physiology
  • Synaptic Transmission / physiology

Substances

  • LDL-Receptor Related Proteins
  • Lrp4 protein, mouse
  • Receptors, Cholinergic
  • Receptors, LDL
  • MuSK protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • Acetylcholine