Abstract
We have collected additional information using four brevetoxin derivatives, which supports our hypothesis of the orientation of the brevetoxin molecule in the voltage-sensitive sodium channel. Of the four things that natural brevetoxins induce, that being (1) shifting the activation potential to more negative values (i.e. channels are open at membrane potentials when they should be closed), (2) inducing a channel sub-type with modified conductance kinetics (slowed kinetics of ion transport), (3) inducing prolonged mean open times in channels (once channels are open they stay open), and (4) inhibiting inactivation (channels cannot progress from open-inactivated state), we have now produced toxins that do not possess all four characteristics. Thus, we believe we have begun to uncouple these activities from one another using synthetic organic chemistry.