From a pump to a pore: how palytoxin opens the gates.

Abstract

The ion channel field has benefited enormously from a plethora of natural toxins that target specific ion channels (1–13), and those toxins continue to be key molecular tools in the postgenomics era. The ion transporter field has not been so lucky, in general. Its arsenal of specific toxins is much more limited, perhaps because it's not so easy to bring one's prey, or biological enemy, quickly to its knees by inhibiting an ion transporter or an ion pump. However, the Na/K pump, which establishes the normal sodium and potassium gradients across the outer membranes of most animal cells, is an exception. The Na/K pump is the specific target of two types of natural toxins, heart glycosides (14, 15) and palytoxin (16–18). Although heart glycosides will be well known to the great majority of readers, palytoxin is likely to be obscure. Long deserving of more careful attention, a careful functional analysis of palytoxin actions presented in this issue of PNAS by Artigas and Gadsby (19) takes an important step to pick up the slack.