title: Sublytic complement attack increases intracellular sodium in rat skeletal muscle.
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.
  
  
  METHODS
  Fast-twitch extensor digitorum longus muscles were freshly isolated from infant rats. Unsensitized muscles were incubated at 30 degrees C for 60 min in the media containing 10% 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.
authors.affiliation: Laboratories for Surgical Metabolism and Nutrition, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Rounds
authors.forename: E
authors.initials: E
authors.lastname: Chambers
authors.forename: D O
authors.initials: DO
authors.lastname: Jacobs
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003186:Complement C9 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D003170:Complement Pathway, Alternative / Q000187:drug effects / Q000276:immunology*; D003171:Complement Pathway, Classical / Q000187:drug effects / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000276:immunology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D009929:Organ Size; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*
chemical_list: D003186:Complement C9; D015938:Complement Membrane Attack Complex; D004791:Enzyme Inhibitors; D010042:Ouabain; D000255:Adenosine Triphosphate; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D011188:Potassium