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Updated: Sep 1, 2025

Registration of Calcium Transients in Mouse Neuromuscular Junction with High Temporal Resolution using Confocal Microscopy
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Registration of Calcium Transients in Mouse Neuromuscular Junction with High Temporal Resolution using Confocal Microscopy

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"Calcium bombs" as harbingers of synaptic pathology and their mitigation by magnesium at murine neuromuscular

Kosala N Dissanayake1,2, Robert R Redman1,2, Harry Mackenzie1,2

  • 1Euan MacDonald Centre for Motor Neurone Disease Research, The University of Edinburgh, Edinburgh, United Kingdom.

Frontiers in Molecular Neuroscience
|August 12, 2022
PubMed

Insights

Elevating magnesium ions (Mg2+) can prevent excitotoxicity at neuromuscular junctions (NMJs), a key factor in amyotrophic lateral sclerosis (ALS). This approach mitigates calcium overload and nerve terminal degeneration, offering a potential therapeutic strategy for synaptic pathology.

Area of Science:

  • Neuroscience
  • Toxicology
  • Muscle Physiology

Background:

  • Excitotoxicity is implicated in amyotrophic lateral sclerosis (ALS) pathogenesis.
  • Early ALS signs include motor nerve terminal degeneration at neuromuscular junctions (NMJs).

Purpose of the Study:

  • To investigate excitotoxicity at NMJs using an organophosphorus (OP) compound model.
  • To explore the role of calcium (Ca2+) and the potential of magnesium (Mg2+) in mitigating NMJ pathology.

Main Methods:

  • Utilized isolated mouse muscle exposed to the OP compound omethoate to induce NMJ excitotoxicity.
  • Measured motor endplate contractures and Ca2+ influx ('calcium bombs') using Fluo-4 fluorescence.
  • Assessed NMJ degeneration in nerve-muscle preparations cultured with OP compounds and their metabolites.
  • Investigated the effect of varying extracellular Mg2+ concentrations (1-5 mM) on NMJ responses.

Main Results:

  • Omethoate induced prolonged motor endplate contractures and 'calcium bombs' at NMJs.
  • Increased extracellular Mg2+ (1-5 mM) significantly mitigated both contractures and Ca2+ overload.
  • OP insecticide exposure led to NMJ degeneration, which was also prevented by elevated Mg2+.
  • Demonstrated a strong link between Ca2+ dynamics and NMJ degeneration under excitotoxic conditions.

Conclusions:

  • Elevating extracellular Mg2+ effectively mitigates excitotoxicity-induced 'calcium bombs' and NMJ degeneration.
  • The findings support a role for Ca2+ dysregulation in NMJ pathology relevant to ALS.
  • Suggests that increasing extracellular Mg2+ is a promising therapeutic strategy for synaptic damage caused by excitotoxic triggers.
Keywords:
ALScalcium imagingmuscle contractionneuromuscular junctionorgan culturesynapsesynaptic pathology

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