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Effect of low calcium and protease inhibitors on synapse elimination during postnatal development in the rat soleus

A L Connold, J V Evers, G Vrbová

    Brain Research
    |July 1, 1986
    PubMed

    Insights

    Calcium

    Area of Science:

    • Neuroscience
    • Developmental Biology
    • Muscle Physiology

    Background:

    • Developing skeletal muscle fibers undergo synapse reorganization.
    • Polyneuronal innervation is rapidly reduced in rat soleus muscles between 9 and 12 days.
    • The precise mechanisms driving this synaptic refinement remain under investigation.

    Purpose of the Study:

    • To investigate the role of calcium and calcium-dependent enzymes in the elimination of polyneuronal innervation during neuromuscular junction development.
    • To determine if calcium-activated neutral protease (CANP) is involved in synapse reorganization.

    Main Methods:

    • Electrophysiological and histological techniques were employed.
    • In vivo experiments involved local application of calcium chelators (EGTA, BAPTA) and CANP inhibitors (leupeptin, E-64) to developing rat soleus muscles.
    • Neuromuscular activity and the rate of polyneuronal innervation elimination were assessed.

    Main Results:

    • Reducing local calcium concentration with EGTA or BAPTA significantly slowed the elimination of polyneuronal innervation.
    • This calcium reduction did not substantially decrease neuromuscular activity.
    • Application of CANP inhibitors (leupeptin, E-64) produced similar delays in synapse elimination.

    Conclusions:

    • Calcium plays a crucial role in the developmental reorganization of synaptic inputs to skeletal muscle.
    • Calcium-activated neutral protease (CANP) is implicated as a key enzyme in this calcium-dependent synapse elimination process.
    • These findings highlight CANP's importance in refining the developing neuromuscular junction.

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