Abstract

The effects of palytoxin on squid axon membranes have been studied by means of internal perfusion and voltage clamp techniques. When applied externally at a concentration ranging from 1 X 10(-8) to 1 X 10(-6) M, palytoxin caused a large depolarization of the membrane that was reversed slowly after washing with toxin-free solution. The toxin-induced depolarization disappeared quickly upon decreasing the external sodium concentration from 445 to 1 mM and the membrane was hyperpolarized beyond the original level. Palytoxin did not cause depolarization if both external and internal solutions were devoid of sodium. The toxin-induced depolarization was only reversed partially by external application of 1 X 10(-6) M tetrodotoxin. Palytoxin had no effect on the resting potential when perfused internally. These results indicate that palytoxin acts from outside of the nerve membrane to increase sodium permeability, thereby causing a depolarization. The palytoxin-poisoned membrane was also permeable to other cations with a permeability ratio of Na/Li/Cs/NH4 = 1:0.62:0.75:1.45. Under voltage clamp conditions, palytoxin shifted the voltage dependence of peak sodium current and steady-state potassium current in the direction of hyperpolarization and reduced markedly the maximum amplitude of peak sodium current. However, the kinetics of sodium current underwent little or no change except a shift of voltage dependence toward hyperpolarization. Leakage current increased markedly after application of palytoxin. In view of these observations and data from the literature, it was suggested that palytoxin creates a new channel in the membrane, thereby causing an increase in cation permeability, depolarization, and other effects such as muscle contraction.