Electrophysiological analysis of neuromuscular synaptic function in myasthenia gravis patients and animal models
Study of the electrophysiological function of the neuromuscular junction (NMJ) is instrumental in the understanding of the symptoms and pathophysiology of myasthenia gravis (MG), an autoimmune disorder characterized by fluctuating and fatigable muscle weakness. Most patients have autoantibodies to t...
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| Published in | Experimental neurology Vol. 270; pp. 41 - 54 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.08.2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0014-4886 1090-2430 1090-2430 |
| DOI | 10.1016/j.expneurol.2015.01.007 |
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| Abstract | Study of the electrophysiological function of the neuromuscular junction (NMJ) is instrumental in the understanding of the symptoms and pathophysiology of myasthenia gravis (MG), an autoimmune disorder characterized by fluctuating and fatigable muscle weakness. Most patients have autoantibodies to the acetylcholine receptor at the NMJ. However, in recent years autoantibodies to other crucial postsynaptic membrane proteins have been found in previously ‘seronegative’ MG patients. Electromyographical recording of compound and single-fibre muscle action potentials provides a crucial in vivo method to determine neuromuscular transmission failure while ex vivo (miniature) endplate potential recordings can reveal the precise synaptic impairment. Here we will review these electrophysiological methods used to assess NMJ function and discuss their application and typical results found in the diagnostic and experimental study of patients and animal models of the several forms of MG.
•Electrophysiological methods allow detailed study of neuromuscular synapse function.•Functional characterisation is crucial to understand the pathophysiology of myasthenia.•Electrophysiological assessment of experimental drug effects in models is clinically relevant.•This paper aims to provide guidance for electrophysiological study of myasthenic neuromuscular synapses. |
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| AbstractList | Study of the electrophysiological function of the neuromuscular junction (NMJ) is instrumental in the understanding of the symptoms and pathophysiology of myasthenia gravis (MG), an autoimmune disorder characterized by fluctuating and fatigable muscle weakness. Most patients have autoantibodies to the acetylcholine receptor at the NMJ. However, in recent years autoantibodies to other crucial postsynaptic membrane proteins have been found in previously ‘seronegative’ MG patients. Electromyographical recording of compound and single-fibre muscle action potentials provides a crucial in vivo method to determine neuromuscular transmission failure while ex vivo (miniature) endplate potential recordings can reveal the precise synaptic impairment. Here we will review these electrophysiological methods used to assess NMJ function and discuss their application and typical results found in the diagnostic and experimental study of patients and animal models of the several forms of MG.
•Electrophysiological methods allow detailed study of neuromuscular synapse function.•Functional characterisation is crucial to understand the pathophysiology of myasthenia.•Electrophysiological assessment of experimental drug effects in models is clinically relevant.•This paper aims to provide guidance for electrophysiological study of myasthenic neuromuscular synapses. Study of the electrophysiological function of the neuromuscular junction (NMJ) is instrumental in the understanding of the symptoms and pathophysiology of myasthenia gravis (MG), an autoimmune disorder characterized by fluctuating and fatigable muscle weakness. Most patients have autoantibodies to the acetylcholine receptor at the NMJ. However, in recent years autoantibodies to other crucial postsynaptic membrane proteins have been found in previously 'seronegative' MG patients. Electromyographical recording of compound and single-fibre muscle action potentials provides a crucial in vivo method to determine neuromuscular transmission failure while ex vivo (miniature) endplate potential recordings can reveal the precise synaptic impairment. Here we will review these electrophysiological methods used to assess NMJ function and discuss their application and typical results found in the diagnostic and experimental study of patients and animal models of the several forms of MG.Study of the electrophysiological function of the neuromuscular junction (NMJ) is instrumental in the understanding of the symptoms and pathophysiology of myasthenia gravis (MG), an autoimmune disorder characterized by fluctuating and fatigable muscle weakness. Most patients have autoantibodies to the acetylcholine receptor at the NMJ. However, in recent years autoantibodies to other crucial postsynaptic membrane proteins have been found in previously 'seronegative' MG patients. Electromyographical recording of compound and single-fibre muscle action potentials provides a crucial in vivo method to determine neuromuscular transmission failure while ex vivo (miniature) endplate potential recordings can reveal the precise synaptic impairment. Here we will review these electrophysiological methods used to assess NMJ function and discuss their application and typical results found in the diagnostic and experimental study of patients and animal models of the several forms of MG. Study of the electrophysiological function of the neuromuscular junction (NMJ) is instrumental in the understanding of the symptoms and pathophysiology of myasthenia gravis (MG), an autoimmune disorder characterized by fluctuating and fatigable muscle weakness. Most patients have autoantibodies to the acetylcholine receptor at the NMJ. However, in recent years autoantibodies to other crucial postsynaptic membrane proteins have been found in previously 'seronegative' MG patients. Electromyographical recording of compound and single-fibre muscle action potentials provides a crucial in vivo method to determine neuromuscular transmission failure while ex vivo (miniature) endplate potential recordings can reveal the precise synaptic impairment. Here we will review these electrophysiological methods used to assess NMJ function and discuss their application and typical results found in the diagnostic and experimental study of patients and animal models of the several forms of MG. |
| Author | Plomp, Jaap J. Morsch, Marco Verschuuren, Jan J.G.M. Phillips, William D. |
| Author_xml | – sequence: 1 givenname: Jaap J. surname: Plomp fullname: Plomp, Jaap J. email: j.j.plomp@lumc.nl organization: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands – sequence: 2 givenname: Marco surname: Morsch fullname: Morsch, Marco organization: Motor Neuron Disease Research Group, Macquarie University, Sydney, Australia – sequence: 3 givenname: William D. surname: Phillips fullname: Phillips, William D. organization: Physiology and Bosch Institute, University of Sydney, Sydney, Australia – sequence: 4 givenname: Jan J.G.M. surname: Verschuuren fullname: Verschuuren, Jan J.G.M. organization: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25620417$$D View this record in MEDLINE/PubMed |
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| Keywords | Synapse Myasthenia gravis Mouse models Compound muscle action potential Electrophysiology Electromyography Endplate Muscle-specific kinase Neuromuscular junction Acetylcholine receptor |
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| SubjectTerms | Acetylcholine receptor Animals Compound muscle action potential Disease Models, Animal Electromyography Electrophysiology Endplate Humans Mouse models Muscle-specific kinase Myasthenia gravis Myasthenia Gravis - physiopathology Neuromuscular junction Neuromuscular Junction - anatomy & histology Neuromuscular Junction - physiology Synapse Synaptic Transmission - physiology |
| Title | Electrophysiological analysis of neuromuscular synaptic function in myasthenia gravis patients and animal models |
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