Calcium dependence of damage to mouse motor nerve terminals following oxygen/glucose deprivation

Janet D. Talbot, Gavriel David, Ellen F. Barrett, John N. Barrett

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Abstract

Motor nerve terminals are especially sensitive to an ischemia/reperfusion stress. We applied an in vitro model of this stress, oxygen/glucose deprivation (OGD), to mouse neuromuscular preparations to investigate how Ca 2+ contributes to stress-induced motor terminal damage. Measurements using an ionophoretically-injected fluorescent [Ca 2+] indicator demonstrated an increase in intra-terminal [Ca 2+] following OGD onset. When OGD was terminated within 20-30min of the increase in resting [Ca 2+], these changes were sometimes reversible; in other cases [Ca 2+] remained high and the terminal degenerated. Endplate innervation was assessed morphometrically following 22min OGD and 120min reoxygenation (32.5°C). Stress-induced motor terminal degeneration was Ca 2+-dependent. Median post-stress endplate occupancy was only 26% when the bath contained the normal 1.8mM Ca 2+, but increased to 81% when Ca 2+ was absent. Removal of Ca 2+ only during OGD was more protective than removal of Ca 2+ only during reoxygenation. Post-stress endplate occupancy was partially preserved by pharmacological inhibition of various routes of Ca 2+ entry into motor terminals, including voltage-dependent Ca 2+ channels (ω-agatoxin-IVA, nimodipine) and the plasma membrane Na +/Ca 2+ exchanger (KB-R7943). Inhibition of a Ca 2+-dependent protease with calpain inhibitor VI was also protective. These results suggest that most of the OGD-induced motor terminal damage is Ca 2+-dependent, and that inhibition of Ca 2+ entry or Ca 2+-dependent proteolysis can reduce this damage. There was no significant difference between the response of wild-type and presymptomatic superoxide dismutase 1 G93A mutant terminals to OGD, or in their response to the protective effect of the tested drugs.

Original languageEnglish (US)
Pages (from-to)95-104
Number of pages10
JournalExperimental neurology
Volume234
Issue number1
DOIs
StatePublished - Mar 1 2012

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Keywords

  • Calcium
  • Calpain
  • Hypoxia
  • Motor nerve terminal
  • Mouse
  • Muscle endplate
  • Na /Ca exchanger
  • Oxygen/glucose deprivation
  • SOD1-G93A
  • Superoxide dismutase 1

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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