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Synaptic transmission blockade increases plasminogen activator activity in mouse skeletal muscle poisoned with botulinum toxin type A
Author(s) -
Tian WenHao,
Festoff Barry W.,
Blot Stéphane,
Diaz Jorge,
Hantaï Daniel
Publication year - 1995
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890200105
Subject(s) - reinnervation , denervation , botulinum toxin , neuromuscular transmission , chemistry , acetylcholine , endocrinology , medicine , skeletal muscle , axotomy , plasminogen activator , anatomy , biology , neuroscience , central nervous system
Experimental denervation, either by nerve crush or axotomy, leads to a dramatic increase in muscle plasminogen activator (PA) activity, suggesting a regulation of muscle PA levels by some neural influence (Festoff et al., 1986, J. Cell Biol., 103:1415–1421; Hantaï et al., 1990, Proc. Natl. Acad. Sci. U.S.A., 87:2926–2930). The Botulinum toxin (BoTx) type A is known to selectively interrupt the release of acetylcholine without structurally altering synaptic morphology. In the present study we have used acute BoTx poisoning of hind limb muscles to further explore the neural regulation of muscle PA activities directly after poisoning and during the process of collateral reinnervation. Electromyographic recording and study of ultraterminal sprouting after zinc iodideosmium and silver‐cholinesterase staining were used to monitor “denervation” and reinnervation. Muscle choline acetyltransferase activity did not decrease, as is observed after experimental denervation, but in contrast increased and, therefore, reflected the functional integrity of intramuscular nerve endings. Within 2 days of BoTx poisoning, muscle urokinase‐PA, and to a lesser extent, tissue‐PA activities, rose in muscle extracts as shown by an amidolytic assay and fibrin zymography. When reinnervation occurred, muscle urokinase‐PA activity decreased but did not return to baseline levels within the 80 days of our study. These results suggest that cholinergic transmission‐regulated events determine activity of muscle PAs and that PAs likely have a role in neuromuscular formation and plasticity. © 1995 Wiley‐Liss, Inc.