This study investigated the mode of action of conantokin-T, a 21 amino acid 
peptide toxin isolated from the venom of the fish-hunting cone snail Conus 
tulipa, on excitatory synaptic transmission in rat hippocampal slices using 
intracellular recording techniques. Superfusion of conantokin-T (1-500 nM) 
specifically and irreversibly decreased the pharmacologically isolated 
N-methyl-D-aspartate receptor (NMDA)-mediated excitatory postsynaptic potential 
(EPSPNMDA) in a concentration-dependent manner but had no effect on normal 
excitatory synaptic transmission (EPSP). The sensitivity of postsynaptic neurons 
to NMDA but not to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid was 
also antagonized by conantokin-T pretreatment. In addition, the 
conantokin-T-induced depression of EPSPNMDA could be antagonized by prior 
treatment of hippocampal slices with either DL-2-amino-5-phosphonovaleate (10 
microM) or ifenprodil (20 microM). However, 7-chlorokynurenic acid (1 microM) 
had no effect on the action of conantokin-T. These findings indicated that 
conantokin-T modulates the NMDA receptor by an interaction with its glutamate 
binding site and polyamine recognition site.