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Antagonism of responses to excitatory amino acids on rat cortical neurones by the spider toxin, argiotoxin 636
Author(s) -
Priestley T.,
Woodruff G.N.,
Kemp J.A.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb12594.x
Subject(s) - kainate receptor , ampa receptor , nmda receptor , spider toxin , excitatory postsynaptic potential , patch clamp , biophysics , agonist , membrane potential , biology , glutamate receptor , chemistry , kainic acid , neuroscience , pharmacology , electrophysiology , receptor , biochemistry
1 Several low molecular weight spider toxins have recently been shown to block potently glutama‐tergic neuromuscular transmission at the invertebrate neuromuscular junction. The aim of the present investigation was to evaluate the effects of one such toxin, argiotoxin 636 , on excitatory amino acid receptor‐mediated responses in mammalian neurones. 2 Membrane currents were recorded from rat cortical neurones after 2–6 weeks in cell culture, by the whole‐cell variant of the patch‐clamp technique. N‐methyl‐D‐aspartate (NMDA) and kainate were used as selective agonists for their respective receptor subtypes. α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid (AMPA) was used as a selective agonist for the quisqualate receptor subtype. 3 Responses to these agonists were characterised with respect to their concentration and voltage‐dependence. Argiotoxin 636 (3–30 μ m ) was found to attenuate markedly responses to NMDA in an agonist‐ and voltage‐dependent manner. Thus, argiotoxin 636 progressively reduced successive responses to NMDA when membrane potentials were voltage clamped between −40 mV to −100 mV. The more negative the membrane potential the more rapid the development of the block of inward current. 4 The antagonism of NMDA‐induced currents by argiotoxin 636 could be reversed by clamping the membrane at positive potentials (+ 20 to + 60 mV) and reapplying NMDA. 5 Responses to AMPA and kainate were less affected by argiotoxin 636 , with an antagonist action only becoming evident at a concentration of 100 μ m6 These results suggest that argiotoxin 636 is an open‐channel blocker of the NMDA activated ion‐channel in mammalian neurones. Furthermore, our results indicate at least a 30 fold selectivity for NMDA over the quisqualate‐ and kainate‐activated ion‐channels.