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Mouse extensor digitorum longus and soleus show distinctive ultrastructural changes induced by veratrine
M A Da Cruz Höfling1, M Dal Pai Silva, E M Silva Freitas
1Department of Histology and Embryology, Institute of Biology, State University of Campinas, SP, Brazil. hofling@obelix.unicamp.br
Journal of Submicroscopic Cytology and Pathology
|November 1, 2002
Summary
Veratrine causes muscle damage by increasing sodium influx, affecting slow-twitch muscles faster than fast-twitch ones. Most damage to muscle fibers repairs within 60 minutes.
Area of Science:
- Muscle physiology
- Cellular biology
- Neurotoxicology
Background:
- Veratrine is a myotoxic agent known to affect muscle fibers.
- Different muscle types (fast-twitch vs. slow-twitch) may exhibit varied responses to myotoxins.
- Understanding the specific cellular mechanisms of veratrine-induced damage is crucial.
Purpose of the Study:
- To investigate the distinct ultrastructural disturbances caused by veratrine in fast-twitch (extensor digitorum longus - EDL) and slow-twitch (soleus - SOL) mouse muscles.
- To determine the time course of these ultrastructural changes.
- To elucidate the role of sodium influx in veratrine-induced myotoxicity.
Main Methods:
- Injection of veratrine into EDL and SOL muscles of mice.
- Ultrastructural analysis of muscle fibers at 15, 30, and 60 minutes post-injection.
- Assessment of mitochondrial, sarcoplasmic reticulum, sarcomere, and sarcolemma integrity.
- Evaluation of the effect of tetrodotoxin pretreatment.
Main Results:
- Mitochondrial swelling occurred earlier in SOL (15 min) than in EDL.
- Sarcoplasmic reticulum swelling and myofilament fragmentation were more pronounced in EDL.
- Hypercontracted sarcomeres and sarcolemmal infoldings were primarily observed in SOL.
- T-tubules remained unaffected; most alterations resolved by 60 minutes.
- Tetrodotoxin pretreatment prevented veratrine-induced damage.
Conclusions:
- Veratrine induces differential ultrastructural damage in fast-twitch and slow-twitch muscles.
- The observed alterations are largely mediated by enhanced sodium influx into muscle fibers.
- Muscle fiber type is a critical factor in determining the response to myotoxic agents like veratrine.