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Related Experiment Videos

Sublytic complement attack increases intracellular sodium in rat skeletal muscle.

K Okamoto1, W Wang, J Rounds

  • 1Laboratories for Surgical Metabolism and Nutrition, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

The Journal of Surgical Research
|May 4, 2000
PubMed
Summary

Complement activation directly alters skeletal muscle sodium levels by forming membrane attack complexes (MACs). This study shows how complement system activation impacts myocellular sodium content in muscle tissue.

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Area of Science:

  • Biochemistry
  • Immunology
  • Physiology

Background:

  • Sepsis is characterized by excessive complement activation and disrupted sodium balance in skeletal muscle.
  • The direct link between complement activation and myocellular sodium changes remains unexamined.

Purpose of the Study:

  • To investigate if sublytic complement activation can directly alter myocellular sodium content.
  • To elucidate the mechanism by which complement affects skeletal muscle sodium homeostasis.

Main Methods:

  • Fast-twitch extensor digitorum longus muscles from infant rats were isolated and incubated with human or rat serum.
  • Complement activation was induced using zymosan, or pathways were inhibited (heat inactivation, C7/C9 deficiency, pathway inhibitors).
  • Intracellular sodium ([Na(+)](i)), potassium ([K(+)](i)), ATP, and LDH release were measured; Na(+)-K(+) ATPase activity was assessed using ouabain.

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Main Results:

  • Normal and activated human serum significantly increased [Na(+)](i) and the [Na(+)](i)/[K(+)](i) ratio in muscles.
  • These cationic changes were abolished by heat inactivation, C7 deficiency, and alternative pathway inhibition.
  • Alterations in [Na(+)](i) correlated with C9 addition, suggesting a role for membrane attack complexes (MACs) and ruling out Na(+)-K(+) pump dysfunction or energy depletion.

Conclusions:

  • Sublytic amounts of MACs, generated during complement activation, directly alter intracellular sodium in ex vivo skeletal muscle.
  • This finding establishes a direct mechanistic link between complement system activity and skeletal muscle sodium regulation.