Dendrotoxin, 4-aminopyridine, and beta-bungarotoxin act at common loci but by two distinct mechanisms to induce Ca2+-dependent release of glutamate from guinea-pig cerebrocortical synaptosomes.
The release of endogenous glutamate from guinea-pig cerebrocortical synaptosomes evoked by dendrotoxin, beta-bungarotoxin, and 4-aminopyridine is compared. Dendrotoxin and 4-aminopyridine cause Ca2+-dependent release, representing a partial depletion of the KCl-releasable transmitter pool. The decrease in the plasma membrane potential caused by 4-aminopyridine or dendrotoxin and the evoked release of glutamate from a transmitter pool accord with the inhibitory action of these agents on certain K+ conductances. In contrast, the massive release of glutamate evoked by beta-bungarotoxin is produced in the presence of Ca2+ but not of Sr2+, a result consistent with a generalised permeabilisation of synaptosomal plasma membranes. Although dendrotoxin inhibits the binding of beta-bungarotoxin and the resultant synaptosomal lysis, demonstration of a direct effect of beta-bungarotoxin binding per se on K+ permeability is impractical owing to its phospholipase A2 activity.
Tibbs
G R
GR
Department of Biochemistry, Imperial College, South Kensington, London, England.
Dolly
J O
JO
Nicholls
D G
DG
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000494:pharmacology*; D005971:Glutamates / Q000493:pharmacokinetics*; D018698:Glutamic Acid; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D013324:Strontium / Q000493:pharmacokinetics; D013574:Synaptosomes / Q000378:metabolism*
D000631:Aminopyridines; D002038:Bungarotoxins; D004546:Elapid Venoms; D005971:Glutamates; D018698:Glutamic Acid; D011189:Potassium Chloride; C020273:dendrotoxin; D015761:4-Aminopyridine; D002118:Calcium; D013324:Strontium