CONANTOKIN-T SELECTIVELY ANTAGONIZES N-METHYL-D-ASPARTATE-EVOKED RESPONSES IN RAT HIPPOCAMPAL SLICE

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 s nail Conus tulipa, on excitatory synaptic transmission in rat hippocam pal slices using intracellular recording techniques. Superfusion of co nantokin-T (1-500 nM) specifically and irreversibly decreased the phar macologically isolated N-methyl-D-aspartate receptor (NMDA)-mediated e xcitatory postsynaptic potential (EPSP(NMDA)) in a concentration-depen dent manner but had no effect on normal excitatory synaptic transmissi on (EPSP). The sensitivity of postsynaptic neurons to NMDA but not to lpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid was also antag onized by conantokin-T pretreatment. In addition, the conantokin-T-ind uced depression of EPSP(NMDA) could be antagonized by prior treatment of hippocampal slices with either DL-2-amino-5-phosphonovaleate (10 mu M) or ifenprodil (20 mu M). However, 7-chlorokynurenic acid (1 mu M) had no effect on the action of conantokin-T. These findings indicated that conantokin-T modulates the NMDA receptor by an interaction with i ts glutamate binding site and polyamine recognition site. (C) 1997 Els evier Science Ltd.