ABSTRACT

No abstract

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.

No abstract

1. To examine the role of the phosphoinositide cascade triggered by disturbed Ca2' homeostasis in ischaemic neurones, inositol 1,3,4,5-tetrakisphosphate (InsP4) was applied to the cytoplasmic face of membrane patches isolated from CAl pyramidal neurones in the gerbil hippocampus. 2. In outside-out recordings, InsP4induced an inward current which was increased by raising the extracellular [Ca2+]. In contrast, no clear channel openings could be observed in patches from neurones of sham-operated gerbils. 3. Open probabilities of InsP4-activated channels were significantly decreased upon application of w-conotoxin but were not affected by wo-agatoxin or nifedipine.4. In inside-out patches using high concentrations of Ca2+, Ba2' or Sr2+ in the pipette solution, InsP4 enhanced inward currents. 5. Application of the isomers of InsP4 slightly enhanced the currents, but inositol 1,4,5-trisphosphate (InsP3) had no effect. 6. In the absence of InsP4 there was a single main Ba2+ current peak of 4 0 pA in amplitude, whereas upon its application two main peaks of 3 0 and 7 2 pA were present. 7. The open probabilities of these channels were apparently increased by InsP4. 8. These findings support the view that a disturbed phosphoinositide cascade occurs in the hippocampal pyramidal neurones after ischaemia and the InsP4 thus formed plays an important role in promoting the CPa2 accumulation which results in neuronal death.