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At least six topologically separated neurotoxin receptor sites
have been identified on sodium channels that reveal strong allosteric
interactions among them. We have studied the allosteric modulation
induced by veratridine, binding to receptor site 2, and brevetoxin
PbTx-1, occupying receptor site 5, on the binding of
Volume 270,
Number 25,
Issue of June 23, pp. 15153-15161, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
-Scorpion
Toxins Binding on Rat Brain and Insect Sodium Channels Reveal Divergent
Allosteric Modulations by Brevetoxin and Veratridine
-scorpion
toxins at receptor site 3, on three different neuronal sodium channels:
rat brain, locust, and cockroach synaptosomes. We used I-AaH II, the most active
-scorpion toxin on
vertebrates, and I-Lqh
IT, shown to have high
activity on insects, as specific probes for receptor site 3 in rat
brain and insect sodium channels. Our results reveal that brevetoxin
PbTx-1 generates three types of effects at receptor site 3: 1) negative
allosteric modulation in rat brain sodium channels, 2) positive
modulation in locust sodium channels, and 3) no effect on cockroach
sodium channel. However, PbTx-1 activates sodium channels in cockroach
axon similarly to its activity in other preparation. Veratridine
positively modulates both rat brain and locust sodium channels but had
no effect on -toxin binding in cockroach. The dramatic differences
in allosteric modulations in each sodium channel subtype suggest
structural differences in receptor sites for PbTx-1 and/or at the
coupling regions with -scorpion toxin receptor sites in the
different sodium channels, which can be detected by combined
application of specific channel modifiers and may elucidate the dynamic
gating activity and the mechanism of allosteric interactions among
various neurotoxin receptors.
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