dizocilpine-maleate and agatoxin-489

Agatoxin-489, extracted from the venom of the Agelenopsis aperta spider, was studied on acutely isolated perfused hippocampal neurons of rat using the concentration clamp technique. Agatoxin-489 proved to be a selective N-methyl-D-aspartate antagonist; responses to applications of N-methyl-D-aspartate or L-aspartate were blocked by concentrations of agatoxin-489 ranging between 0.1 nM and 1 microM, while responses to kainate were not affected by agatoxin-489 at concentrations up to 10 microM. The actions of agatoxin-489 against responses to N-methyl-D-aspartate or L-aspartate were use- and voltage-dependent, being less pronounced with an increase in the holding potential from -100 to -30 mV. The action of agatoxin-489 could be completely or partially reversed only after washout in the presence of an N-methyl-D-aspartate agonist. The washout was more effective at positive membrane potentials ranging from 0 to +20 mV. These results imply that the spider toxin agatoxin-489, like dizocilpine, is a potent and selective N-methyl-D-aspartate antagonist which preferentially interacts with activated N-methyl-D-aspartate receptors and/or open N-methyl-D-aspartate-activated ionic channels.

Topics: Agatoxins; Animals; Aspartic Acid; Dizocilpine Maleate; Dose-Response Relationship, Drug; Evoked Potentials; Glutamates; Glutamic Acid; Hippocampus; In Vitro Techniques; Kainic Acid; Membrane Potentials; N-Methylaspartate; Neurons; Neurotoxins; Polyamines; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Spiders