TETRODOTOXIN REVERSES BREVETOXIN ALLOSTERIC INHIBITION OF SCORPION ALPHA-TOXIN BINDING ON RAT-BRAIN SODIUM-CHANNELS

Voltage-sensitive sodium channels are responsible for the initiation o f action potentials in many excitable cells, Several neurotoxins bind to distinct receptor sites on sodium channels and reveal strong allost eric interactions among them, Scorpion alpha toxins, which inhibit sod ium channel inactivation by binding to receptor site 3, have been very important tools to study sodium channel structure and function, Recen tly, we have shown that brevetoxin induce a strong negative allosteric modulation on scorpion alpha-toxin binding on rat brain sodium channe ls, in contrast to previously published studies. In this report we hav e examined the reasons for this discrepancy and found new, unexpected allosteric interactions between the tetrodotoxin and brevetoxin recept or sites, using scorpion alpha-toxin as sensitive probe for subtle con formational changes on sodium channels. Tetrode-toxin reverses the neg ative modulation induced by brevetoxin on scorpion alpha-toxin binding , revealing new dynamic interactions in sodium channel structure.