Palytoxin: Membrane Mechanisms of Action

Palytoxin is a marine toxin originally isolated from the zoantharians of the genus Palythoa, but now is found in marine organisms ranging from dinoflagellates to fishes. With a MW of 2680, it is one of the largest nonpolymeric natural products ever found. Its complex structure has been elucidated and total synthesis has been achieved. With an LD(50) of 25 ng/kg for rabbits (the most sensitive species), it is one of the most lethal marine toxins. It binds to the Na,K-ATPase specifically with a K(D) of 20 pM. It has a unique action on the Na,K-ATPase, converting the pump into an ion channel and resulting in K(+) efflux, Na(+) influx and membrane depolarization. As a result palytoxin causes a wide spectrum of secondary pharmacological actions. By acting like a key to unlock the internal structure of the Na,K-ATPase, palytoxin holds promise as a useful tool for investigation of the pump molecule.