Botulinum toxin type A inhibits Ca(2+)-dependent transport of acetylcholine in reconstituted giant liposomes made from presynaptic membranes from cholinergic nerve terminals.
Giant liposomes were made from a mixture of asolectin phospholipid vesicles and presynaptic plasma membranes isolated from Torpedo cholinergic nerve endings. Acetylcholine filled giant liposomes were able to release neurotransmitter upon stimulation by the Ca2+ ionophore A23187 and Ca2+. Botulinum neurotoxin type A inhibited this Ca(2+)-dependent acetylcholine transport. Additionally, Botulinum toxin type A decreased membrane fluidity of liposomes. These results suggest that Botulinum toxin can interact directly with components of the presynaptic plasma membrane and inhibit acetylcholine translocation. Furthermore, since the reconstituted liposomes do not have synaptic vesicle components, the observed effects may account for the action of Botulinum toxin on the non-quantal release of acetylcholine from motor nerve terminals.
López-Alonso
E
E
Department of Neurochemistry, University of Alicante, Spain.
Canaves
J
J
Arribas
M
M
Casanova
A
A
Marsal
J
J
González-Ros
J M
JM
Solsona
C
C
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001905:Botulinum Toxins / Q000633:toxicity*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000378:metabolism*; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects; D013696:Temperature; D013997:Time Factors; D014101:Torpedo
D008081:Liposomes; D000001:Calcimycin; D001905:Botulinum Toxins; D000109:Acetylcholine; D002118:Calcium