Pumiliotoxin B binds to a site on the voltage-dependent sodium channel that is allosterically coupled to other binding sites.
Pumiliotoxin B (PTX-B), an alkaloid that has cardiotonic and myotonic activity, increases sodium influx in guinea pig cerebral cortical synaptoneurosomes. In the presence of scorpion venom (Leiurus) or purified alpha-scorpion toxin, the PTX-B-induced sodium influx is enhanced severalfold. PTX-B alone has no effect on sodium flux in N18 neuroblastoma cells but, in the presence of alpha-scorpion toxin, stimulation of sodium influx by PTX-B reaches levels comparable to that attained with the sodium channel activator veratridine. In neuroblastoma LV9 cells, a variant mutant that lacks sodium channels, neither veratridine nor PTX-B induces sodium fluxes in either the presence or absence of alpha-scorpion toxin. In synaptoneurosomes and in N18 cells, the sodium influx induced by the combination of PTX-B and alpha-scorpion toxin is inhibited by tetrodotoxin and local anesthetics. PTX-B does not interact with two of the known toxin sites on the sodium channel, as evidenced by a lack of effect on binding of [3H]saxitoxin or [3H]batrachotoxinin A benzoate to brain synaptoneurosomes. Synergistic effects on sodium influx with alpha-scorpion toxin, beta-scorpion toxin, and brevetoxin indicate that PTX-B does not interact directly with three other toxin sites on the sodium channel. Thus, PTX-B appears to activate sodium influx by interacting with yet another site on the voltage-dependent sodium channel, a site that is coupled allosterically to sites for alpha-scorpion toxin, beta-scorpion toxin, and brevetoxin.
D000470:Alkaloids / Q000378:metabolism* / Q000494:pharmacology; D000495:Allosteric Site; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D004347:Drug Interactions; D006168:Guinea Pigs; D007212:Indolizines; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009447:Neuroblastoma; D010880:Piperidines; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical; D013574:Synaptosomes / Q000378:metabolism; D014118:Toxins, Biological / Q000494:pharmacology
D000470:Alkaloids; D000779:Anesthetics, Local; D007212:Indolizines; D007473:Ion Channels; D010880:Piperidines; D014118:Toxins, Biological; C031598:pumiliotoxin B; D012964:Sodium