Palytoxin. Recent electrophysiological and pharmacological evidence for several mechanisms of action

1. Palytoxin is one of the most potent toxins known so far. It acts as an haemolysin and alters the functioning of excitable cells. 2. A primary action of palytoxin in excitable cells is to induce the activity of a small conductance (9-25 pS), non-selective cationic channel which then triggers secondary activations of voltage dependent Ca2+ channels and of Na+/Ca2+ exchange. This results in neurotransmitter release by nerve terminals and contractions of striated and smooth muscle cells. 3. Palytoxin induced channels are blocked by amiloride derivatives such as 3,4 dichlorobenzamil. They are also blocked by ouabain but at concentrations higher than those required to inhibit the (Na+,K+)ATPase. 4. A second and independent action of palytoxin is to open a membrane conductive pathway for H+ that drives H+ inside the cells and secondarily activates Na+/H+ exchange activity. 5. A third action of PTX in chick cardiomyocytes is to raise [Ca2+]i in a manner independent of its depolarizing action or of its action on intracellular pH. 6. It is suggested that PTX probably has more than one site of action in excitable cells and that it may act as an agonist for a family of low conductance channels that conduct Na+/K+, H+ and Ca2+ions.