The
alkaloid pumiliotoxin B (PTX-B) "activates" voltage-dependent
sodium channels in synaptoneurosomes and
neuroblastoma cells. It appears that PTX-B activates
sodium channels by interacting with a site that is allosterically coupled to other sites on the
sodium channel, namely two
scorpion toxin sites and the
brevetoxin site. In guinea pig cortical synaptoneurosomes,
alpha-scorpion toxin,
beta-scorpion toxin, and
brevetoxin induce a dose-dependent potentiation of PTX-B-induced 22Na+ influx. The synergism with
beta-scorpion toxin differentiates PTX-B from the
alkaloid veratridine, which induces an activation of
sodium channels that is not affected by
beta-scorpion toxin. PTX-B does not inhibit [3H]batrachotoxinin-A
benzoate ([3H]
BTX-B) binding to the
alkaloid site on
sodium channels. On the other hand,
aconitine, which activates
sodium channels and inhibits [3H]
BTX-B binding, induces a 22Na+ influx that, like PTX-B-induced 22Na+ influx, is potentiated by
alpha-scorpion toxin,
beta-scorpion toxin, and
brevetoxin. Inhibition of [3H]
BTX-B binding by
aconitine is reduced in the presence of PTX-B. Both a type I
pyrethroid (
allethrin) and a type II
pyrethroid (
fenvalerate) inhibit PTX-B- and PTX-B/
alpha-scorpion toxin-mediated 22Na+ influx.
Allethrin and
fenvalerate also inhibit
aconitine-mediated 22Na+ flux but not BTX-mediated 22Na+ influx. It is proposed that on the
sodium channel there is an "
alkaloid-binding domain" at which
alkaloids exert stimulatory actions. However, depending on the region on the domain to which the binding occurs, different allosteric interactions with other sites can be observed. PTX-B is proposed to interact with a part of the
alkaloid-binding domain that is shared by
aconitine but not by batrachotoxin or
veratridine, whereas
aconitine interacts with a part of the domain shared by PTX-B and by batrachotoxin/
veratridine.