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Light chain of botulinum neurotoxin is active in mammalian motor nerve terminals when delivered via liposomes
Author(s) -
de Paiva Anton,
Oliver Dolly J.
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80836-8
Subject(s) - liposome , immunoglobulin light chain , neurotoxin , neuromuscular transmission , neuromuscular junction , biophysics , chemistry , motor nerve , toxin , neurotransmission , 4 aminopyridine , botulinum neurotoxin , botulinum toxin , pharmacology , biochemistry , biology , neuroscience , antibody , immunology , endocrinology , receptor , potassium channel
Liposomal encapsulation of the individual light and heavy chain of botulinum neurotoxin A was used to investigate their intra‐cellular effects on synaptic transmission at the murine neuromuscular junction. Bath‐application to phrenic nerve‐hemidiaphragms of liposomes containing heavy chain (up to 75 nM) caused no alteration in neurally‐evoked muscle tension. In contrast, liposomes with entrapped light chain (9–20 nM final concentration) gave a pre‐synaptic blockade of neuromuscular transmission that could be relieved temporarily by 4‐aminopyridine, as for the dichain toxin. Any contribution from contaminating intact toxin was excluded both by the purity and minimal toxicity in mice of the light chain preparations used, and by the lack of neuromuscular paralysis seen with liposomes containing the maximum amount of native toxin that could have been present in the light chain liposomes. As bath‐application of high concentrations of light chain in the absence of liposomes failed to affect neurotransmiter release, it is concluded that this chain alone can mimic the action of the whole toxin inside mammalian motor nerve endings, its predominant site of action. Thus, light chain could provide a more effective probe for an intra‐cellular component concerned with Ca 2+ ‐dependent secretion.