Electrophysiological analysis of the presynaptic action of beta-bungarotoxin in the central nervous system.
In view of previously reported actions of beta-bungarotoxin (beta-BuTX) on central brain synaptosomes, the effects on this toxin on the electrical activity of two brain slice preparations have been examined in vitro. beta-BuTX initially suppresses the synaptic component of the field responses to electrical stimulation in olfactory cortex and hippocampal slices. Intracellular recordings demonstrate that this synaptic depression occurs without detectable reduction in the sensitivity of the postsynaptic neuron to putative neurotransmitters. Following longer exposure to the toxin, reduced neuronal excitability is observed both pre- and post-synaptically. Elimination of the phospholipase A2 activity of beta-BuTX, by chemical modification or removing the Ca2+ necessary for enzymic activity, greatly reduces but does not totally eradicate the toxin's ability to block neurotransmission in the olfactory cortex. In the absence of enzymic activity beta-BuTX has no obvious effect on axonal conduction. Pure phospholipases A2, such as that from Naja melanoleuca mimic the transmission-blocking action of beta-BuTX, but with lower potency and without the effects on fibre excitability. Collectively, these results are taken as evidence that beta-BuTX initially suppresses transmitter release, a notion supported by the observed loss of spontaneous synaptic activity in hippocampal cells. Prolonged exposure to the toxin induces apparently less specific effects on neuronal excitability which are dependent on phospholipase A2 activity and are discussed with reference to the selective action of beta-BuTX on hippocampal fibre systems which possess release sites.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002038:Bungarotoxins / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000502:physiology; D006168:Guinea Pigs; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*
D002038:Bungarotoxins