Editorial review: Palytoxin: mechanism of action of a potent marine toxin

Palytoxin, the most potent marine toxin known, causes death at doses as low as 0.025 μg/kg. Its chemical structure contains no identifiable subunits, making it one of the most complex natural products known. It exhibits a wide variety of pharmacological actions Including stimulating release of K⁺ from various cell types; depolarization of excitable membranes; contraction of smooth muscle; cardiovascular effects; hemolysis; histamine, prostaglandin and norepinephrine release; platelet aggregation and bone resorption. It also exhibits Inhibition of sperm motility, anti-tumor activity and tumor-promoting activity. Studies on the molecular mechanism of action have led to several proposed mechanisms. The most extensively studied is the proposal that palytoxin interacts with (Na⁺,K⁺)-ATPase at the ouabain binding site, but rather than inhibiting the ion pump as ouabain does, it converts it to an open ion channel, resulting in collapse of ion gradients across the cell membrane. Other possible mechanisms include a similar effect on the acetylcholine receptor, other types of ionophore activity, and release of an endogenous mediator. Many of the pharmacological effects of palytoxin are of types that are mediated by elevated intracellular Ca²⁺. Palytoxin causes elevated intracellular Ca²⁺, but it is not known if it is a direct result of opened ion channels or an indirect effect of altered Na⁺ concentrations.