Presynaptic failure of neuromuscular transmission and synaptic remodeling in EA2

Ricardo A Maselli, J. Wan, V. Dunne, M. Graves, R. W. Baloh, R. L. Wollmann, J. Jen

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Objective: To further investigate the basis of abnormal neuromuscular transmission in two patients with congenital myasthenic syndrome associated with episodic ataxia type 2 (EA2) using stimulated single fiber EMG (SFEMG) and in vitro microelectrode studies. Methods: Two patients with genetically characterized EA2 previously shown to have abnormal neuromuscular transmission by voluntary SFEMG were studied with stimulated SFEMG and anconeus muscle biopsy with microelectrode studies and electron microscopy of the neuromuscular junction. Results: In vivo stimulated SFEMG showed signs of presynaptic failure, with jitter and blocking that improved with increased stimulation frequency. Additional evidence of presynaptic failure was provided by the in vitro microelectrode studies, which showed marked reduction of the end plate potential quantal content in both patients. Of note, the end plate potentials showed high sensitivity to N-type blockade with ωconotoxin not seen in controls. The ultrastructural studies revealed some evidence of small nerve terminals apposed to normal or mildly overdeveloped postsynaptic membranes, suggesting an ongoing degenerative process. Conclusions: The authors demonstrated presynaptic failure of neurotransmission in patients with heterozygous nonsense mutations in CACNA1A. The contribution of non-P-type calcium channels to the process of neurotransmitter release in these patients likely represents a compensatory mechanism, which is insufficient to restore normal neuromuscular transmission.

Original languageEnglish (US)
Pages (from-to)1743-1748
Number of pages6
JournalNeurology
Volume61
Issue number12
StatePublished - Dec 23 2003

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Synaptic Transmission
Microelectrodes
Excitatory Postsynaptic Potentials
Congenital Myasthenic Syndromes
Conotoxins
Neuromuscular Junction
Nonsense Codon
Calcium Channels
Neurotransmitter Agents
Electron Microscopy
Type 2 Episodic Ataxia
Biopsy
Muscles
Membranes
In Vitro Techniques

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Maselli, R. A., Wan, J., Dunne, V., Graves, M., Baloh, R. W., Wollmann, R. L., & Jen, J. (2003). Presynaptic failure of neuromuscular transmission and synaptic remodeling in EA2. Neurology, 61(12), 1743-1748.

Presynaptic failure of neuromuscular transmission and synaptic remodeling in EA2. / Maselli, Ricardo A; Wan, J.; Dunne, V.; Graves, M.; Baloh, R. W.; Wollmann, R. L.; Jen, J.

In: Neurology, Vol. 61, No. 12, 23.12.2003, p. 1743-1748.

Research output: Contribution to journalArticle

Maselli, RA, Wan, J, Dunne, V, Graves, M, Baloh, RW, Wollmann, RL & Jen, J 2003, 'Presynaptic failure of neuromuscular transmission and synaptic remodeling in EA2', Neurology, vol. 61, no. 12, pp. 1743-1748.
Maselli RA, Wan J, Dunne V, Graves M, Baloh RW, Wollmann RL et al. Presynaptic failure of neuromuscular transmission and synaptic remodeling in EA2. Neurology. 2003 Dec 23;61(12):1743-1748.
Maselli, Ricardo A ; Wan, J. ; Dunne, V. ; Graves, M. ; Baloh, R. W. ; Wollmann, R. L. ; Jen, J. / Presynaptic failure of neuromuscular transmission and synaptic remodeling in EA2. In: Neurology. 2003 ; Vol. 61, No. 12. pp. 1743-1748.
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