Does palytoxin open a sodium-sensitive channel in cardiac muscle?

The effect of palytoxin (PTX) on transmembrane potentials and currents of frog atrial fibres was studied using the double sucrose gap technique. PTX irreversibly depolarized the membrane. This depolarization was reversed only when Na ions were removed from the Ringer solution and replaced by a non-permeant cation such as choline. The depolarization was tetrodotoxin (TTX) insensitive and a function of the external Na concentration. In voltage clamp experiments PTX induced the development of a large inward resting current which did not inactivate and was insensitive to ouabain and to a lowering of the temperature. PTX and ouabain did not share the same receptor. Dose-response curves indicated a stoichiometry of 2, which suggested the aggregation of 2 molecules of PTX to form a channel. The channel formed by PTX remained insensitive to TTX, 4 aminopyridine, tetramethyl-ammonium, Cs and Cd, the classical blockers of Na, K and Ca conductances. PTX reduced the Na current, but not the apparent reversal potential for Na ions. It was concluded that PTX might act on frog atrial fibres as a Na ionophore.