Author/Editor     Sket, D; Dettbarn, WD; Clinton, ME; Misulis, KE; Sketelj, J; Čuček, D; Brzin, M
Title     Prevention of diisopropylphosphorofluoridate-induced myopathy by botulinum toxin type A blockage of quantal release of acetycholine
Type     članek
Source     Acta Neuropathol (Berl)
Vol. and No.     Letnik 82, št. 2
Publication year     1991
Volume     str. 134-42
Language     eng
Abstract     Botulinum toxin type A (BTx), which blocks quantal and partially reduces spontaneous nonquantal acetylcholine (ACh) release at neuromuscular junctions, was tested for its possible attenuating effect on diisopropylphosphorofluoridate (DFP)-induced muscle lesions. The extent of muscle lesion in extensor digitorum longus and soleus muscle of DFP injected rats with and without BTx pretreatment was evaluated using light and electron microscopic procedures. In parallel experiments, acetylcholinesterase (AChE) activity was measred and the functional state of muscles in experimental groups was determined by electrophysiological methods. The results show that pretreatment with BTx almost eompletely protects the museles from DFPinduced spontaneous activity and lesions in spite of critically inhibited synaptic AChE. These results are consistent with the conclusion that the effect is not mediated by direct action of organophosph te on muscle, but by the accumulation of ACh resulting in muscle hyperactivity. Therefore, it is coneluded that in conditions of acutely inhibited synaptic AChE, the quantal release of ACh is essential for lesion induction, whereas the spontaneous nonejuantal ACh release, which is only partially affected in BTx-blocked nerve endings, seems not to be involved.
Descriptors     MUSCLES
NEUROMUSCULAR JUNCTION
PARASYMPATHOLYTICS
SYNAPSES
ACETYLCHOLINE
ACETYLCHOLINESTERASE
BOTULINUM TOXINS
ISOFLUROPHATE
ELECTROMYOGRAPHY
ISOFLUROPHATE
MICROSCOPY, ELECTRON
MUSCLES
NECROSIS
NEUROMUSCULAR JUNCTION
RATS
RATS, INBRED STRAINS
SYNAPSES