Effects of a spider toxin and its analogue on glutamate-activated currents in the hippocampal CA1 neuron after ischemia.
1. We studied the effects of polyamine toxins derived from a spider venom on CA1 pyramidal neurons in gerbil hippocampal slices by patch-clamp recording. Joro spider toxin (JSTX) and its synthetic analogue, 1-naphthyl acetyl spermine (Naspm), which are known to block non-N-methyl-D-aspartate (non-NMDA) receptor in a subunit specific manner, were used. 2. Naspm depressed the excitatory postsynaptic currents (EPSCs) mediated by non-NMDA receptor channels. A further reduction of EPSCs occurred with addition of 6-cyano-7-nitroquin-oxaline-2,3- dione (CNQX). Conversely, when CNQX was applied first, no further depression of EPSCs occurred on addition of Naspm, indicating that Naspm blocks a fraction of the CNQX-sensitive non-NMDA-receptor-mediated currents. 3. After ischemia, the time course of EPSCs of CA1 pyramidal neurons was slowed and Naspm depressed the slow EPSCs more strongly than those in control neurons. 4. Analysis of single-channel currents by outside-out patch-clamp recording from ischemic CA1 neurons revealed that Naspm blocked a subpopulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate- and kainate-induced single-channel currents. 5. Because the EPSCs in CA1 neurons after ischemia are mediated by Ca(2+)-permeable non-NMDA receptor-mediated conductances, the present results indicate that Naspm and JSTX are effective at blocking abnormal EPSCs that may induce Ca2+ accumulation leading to delayed neuronal death after transient ischemic insult.
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000502:physiology; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005849:Gerbillinae; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D013111:Spider Venoms / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; C044936:JSTX spider toxin; D009498:Neurotoxins; D013111:Spider Venoms; D018698:Glutamic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid; D002118:Calcium