The in vivo effect of lipopolysaccharide on neuromuscular transmission in the mouse.
The in vivo effect of lipopolysaccharide (endotoxin) on nerve-evoked muscle contractions and neuromuscular transmission was studied in the mouse phrenic nerve-diaphragm preparations. In lipopolysaccharide-treated mouse diaphragms it was observed that indirectly induced twitch tension was unchanged while tetanic tension significantly decreased. Neostigmine (50 nM) increased the amplitude of nerve evoked muscle contractions, while it caused partial fade of tetanic contractions (Wedensky inhibition) and accelerated the run-down of end-plate potentials (e.p.ps) evoked by repetitive nerve stimulation, in the diaphragm of saline-control mice, but not of lipopolysaccharide-treated mice. These effects of neostigmine could be abolished by ouabain (5 microM). Measurement of the quantal contents of e.p.ps revealed that ouabain (5 microM) significantly increased it in the diaphragm of saline-control mice to an extent similar to that in diaphragm of lipopolysaccharide-treated mice. Moreover, ouabain-sensitive Na+, K(+)-ATPase activity in the sciatic nerve of lipopolysaccharide-treated mice was markedly decreased. The alterations in neuromuscular transmission of the diaphragm during endotoxemia could be reversed by the administration of polymyxin B (a lipopolysaccharide neutralizer) and NG-nitro-L-arginine (a nitric oxide (NO) synthase inhibitor), suggesting that NO is involved in these lipopolysaccharide-induced alterations of neuromuscular transmission mediated by an impairment of ouabain-sensitive Na+, K(+)-ATPase activity in mouse motor nerves.
Liu
S H
SH
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei.
Sheu
Z J
ZJ
Lin
R H
RH
Lin-Shiau
S Y
SY
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects / Q000294:innervation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009388:Neostigmine / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects*; D019335:Nitroarginine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D012462:Saline Solution, Hypertonic; D012584:Sciatic Nerve / Q000187:drug effects* / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D010277:Parasympathomimetics; D012462:Saline Solution, Hypertonic; D019335:Nitroarginine; D009388:Neostigmine; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D011112:Polymyxin B