Antiepileptic effect of acylpolyaminetoxin JSTX-3 on rat hippocampal CA1 neurons in vitro

Effects of Spider Venom Toxin PWTX-I (6-Hydroxytrypargine) on the Central Nervous System of Rats

“…I versus V curves carried out before and following the aforementioned experimental protocol indicate that treatment with 6-HT does not significantly alter the membrane potential [Figure 7(III,VI) and Table 1]. The epileptiform activity induced by the perfusion with 0-Mg 2+ ACSF showed in Figure 6(V), stage B is due in part, to the relief of the NMDA receptor channel from the gating effect of Mg 2+ [8]. When 6-HT was applied in this model it was able to amplify epileptiform activity observed in vitro induced by 0-Mg 2+ ACSF [Figure 6(V), stage C].…”

“…For the study of 6-HT in electrophysiology assays, an induced epileptiform activity model based on the removal of the Mg 2+ ions from the ACSF was used in the hippocampal slice perfusion, determining a hyper-excitability state due to the increase of the conductance of Na + and Ca 2+ ions on NMDA-GluRs [7,8]. In addition to this model, the effect of 6-HT administration on hippocampal slices infused with normal ACSF was also investigated with the objective of studying the action of this compound on the basal state of hippocampal neurons.…”

“…Recordings were performed in the target cell on the CA 1 hippocampal layer, by using borosilicate micropipette (electrode impedance 80–100 MΩ) filled with 3 M potassium acetate for intracellular recordings (IC) or ACSF (5–10 MΩ) for extracellular recordings (EC) as previously reported [7,8]. Cyber Amp 380 (Axon Instruments Inc., USA) programmable signal conditioner was used, and current-clamp recordings were performed using an Axoclamp-2B amplifier (AxoClamp 2B, Axon Instruments Inc., Union City, CA, USA).…”

“…Some classes of NPLMM toxins have been reported in spider venoms, such as: (I) acylpolyamines : isolated from the venoms of orb-web-spiders; some of these compounds are neurotoxic and act as antagonists for different subtypes of ionotropic glutamate receptors, whereas others act on nicotinic acetylcholine receptors [5]; these toxins are non-competitive antagonists of glutamate receptors [6], and present neuroprotective actions as previously reported for JSTX-3, which blocks the epileptiform activity in hippocampal CA 1 neurons in vitro [7,8]; (II) bis-(agmatine)-oxamide : isolated from the venom of the “fisher-spider”, Plectreurys tristis [9]; (III) nucleoside-toxins : mono or disulfated nucleoside compounds that are able to block kainate receptors and act on Cav1 calcium channels, such as the toxin HF-6 isolated from the venom of Hololena curta [10]; (IV) tetrahydro-β-carbolines : alkaloid compounds isolated from the venom of the social spider Parawixia bistriata [11] and from the web droplets of the orb-web-spider Nephila clavipes [12]; these compounds are reversible inhibitors of MAO-I and -II of mammals, are lethal to insects and are neurotoxic and convulsivant to rats [13]. …”

“…Another strategy used to characterize the action of neurotoxins in rat brain is the investigation of the effects of these toxins in a model of chronic epilepsy in vitro by using patch-clamp electrophysiology in brain slices [7,22]. …”