Sublytic complement attack increases intracellular sodium in rat skeletal muscle

Ken Okamoto, Weiyang Wang, Jan Rounds, Elizabeth Chambers, Danny O. Jacobs

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background. Although excessive complement activation and deranged sodium homeostasis in skeletal muscle are characteristic in sepsis, their relationship has not been examined. This study was designed to determine if sublytic complement activation can directly mediate changes in myocellular sodium content. Materials and methods. Fast-twitch extensor digitorum longus muscles were freshly isolated from infant rats. Unsensitized muscles were incubated at 36°C for 66 min in the media containing 16% human or rat serum under conditions of no complement activation, activation by zymosan, inactivation by heat, C7 or C9 deficiency, selective inhibition of complement pathway, and inhibition of Na+-K+ ATPase by ouabain. Intracellular sodium ([Na+](i)) and potassium ([K+](i)) contents of the muscles, myocellular ATP, and LDH release from the muscles were then determined. Results. Normal human serum significantly increased [Na+](i) and the [Na+](i)/[K+](i) ratio in the muscles as well as zymosan-activated serum. Heat inactivation, C7 deficiency, and inhibition of the alternative pathway completely abolished the cationic changes. Average LDH release was identical in all groups and less than 6%. Complement activation did not impair ouabain-sensitive Na+-K+ ATPase activity in the muscles or alter myocellular ATP. Thus, the observed alterations are not likely due to dysfunction of Na+-K+ pump or depletion of myocellular energy. Instead, alterations in [Na+](i) were dependent upon the amount of C9 added to C9-deficient serum, which suggests that the alterations are likely dependent on transmembrane pores created by membrane attack complexes (MAC). Conclusions. Sublytic amounts of MAC formed as a result of complement activation can directly alter [Na+](i) in ex vivo skeletal muscle. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)174-182
Number of pages9
JournalJournal of Surgical Research
Volume90
Issue number2
DOIs
StatePublished - May 15 2000

Keywords

  • ATP
  • Complement activation
  • Intracellular sodium
  • Terminal complement complex

ASJC Scopus subject areas

  • Surgery

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