Botulinum neurotoxin and dendrotoxin as probes for studies on transmitter release.
Acceptors for BoNT have been detected autoradiographically on the terminal membrane of motor nerves at a density of approximately 150/micron2 and shown to mediate toxin internalization, a process deemed essential for its inhibition of transmitter release. DTX, a protein with pronounced central neurotoxicity, was shown to induce convulsive states in hippocampal slices from guinea-pig. Synaptic transmission was facilitated and spontaneous epileptiform activity produced in intact cell populations. Voltage clamp analysis of hippocampal neurones revealed that DTX specifically attenuated a transient voltage-dependent K+ conductance (A-current) and this could account for the excitatory effects observed. Proteinaceous acceptors with high affinity for DTX were identified on brain synaptosomal membranes and found to contain a 65 000 Mr polypeptide. Their location in rat brain regions was established and contrasted with that of the binding sites for beta-bungarotoxin. These findings indicate the usefulness of DTX as a probe for a protein associated with one variety of K+ channel while the larger subunit of BoNT was found to interact with a membraneous component that resides at cholinergic nerve terminals and, hence, is likely to have a unique role.
D000818:Animals; D001345:Autoradiography; D001905:Botulinum Toxins / Q000494:pharmacology*; D004546:Elapid Venoms / Q000494:pharmacology*; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects; D051379:Mice; D008854:Microscopy, Electron; D009045:Motor Endplate / Q000648:ultrastructure; D009420:Nervous System / Q000737:chemistry; D009469:Neuromuscular Junction / Q000648:ultrastructure; D009498:Neurotoxins / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000032:analysis* / Q000502:physiology; D013569:Synapses / Q000502:physiology
D004546:Elapid Venoms; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D011950:Receptors, Cholinergic; C020273:dendrotoxin; D001905:Botulinum Toxins