Effects of a Spider Toxin and its Analog on Glutamate-Activated Currents in the Hippocampal CA1 Neuron after Ischemia. Tsubokawa, Hiroshi, Keiji Oguro, Toshio Masuzawa, Terumi Nakajima and Nobufuni Kawai. Department of Physiology and Neurosurgery, Jichi Medical School, Tochigi 329-04, Japan. [grave]aSuntory Institute for Bioorganic Research, Osaka, 618, Japan.
APStracts 2:0039N, 1995.
SUMMARY AND CONCLUSIONS
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 analog, 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- nitroquinoxaline-2,3-dione (CNQX). Conversely, when CNQX was applied first, no further depression of EPSCs occurred upon addition of Naspm, indicating that Naspm blocks a fraction of the CNQX-sensitive non-NMDA receptor-mediated currents. 3. Following 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 (AMPA) and kainate-induced single channel currents. 5. Since the excitatory postsynaptic currents in CA1 neurons following ischemia are mediated by Ca2+- permeable non N-methyl- D -aspartate receptor-mediated conductances, the present results indicate that Naspm and JSTX are effective at blocking abnormal EPSCs which may induce Ca2+ accumulation leading to delayed neuronal death after transient ischemic insult. 

Received 17 October 1994; accepted in final form 21 February 1995.
APS Manuscript Number J641-4.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  3 April 1995.