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 pri mary 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+ channel s and of Na+/Ca2+ exchange. This results in neurotransmitter release b y nerve terminals and contractions of striated and smooth muscle cells . 3. Palytoxin induced channels are blocked by amiloride derivatives s uch as 3,4 dichlorobenzamil. They are also blocked by ouabain but at c oncentrations higher than those required to inhibit the (Na+,K+)ATPase . 4. A second and independent action of palytoxin is to open a membran e conductive pathway for H+ that drives H+ inside the cells and second arily 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 excit able cells and that it may act as an agonist for a family of low condu ctance channels that conduct Na+/K+, H+ and Ca(2+)ions.