The potent depolarizing action of palytoxin isolated from Palythoa tubercurosa on the isolated spinal cord of the frog.

1. The effects of palytoxin (PTX) isolated from Palythoa tubercurosa were tested on the isolated intra-arterially perfused spinal cord of the frog. The resting and evoked potentials were recorded by means of a sucrose-gap technique. 2. PTX caused a marked depolarization of both ventral and dorsal roots. The minimum effective concentration was extremely low, approximately 10(-11) M. During the depolarization the evoked ventral and dorsal root potentials were markedly reduced in amplitude. The ventral root reflex was first augmented and then decreased. 3. The depolarization caused by PTX was markedly reduced when the preparation was perfused with NaCl-deficient medium. However, tetrodotoxin (10(-7) M) only slightly inhibited the depolarization. 4. In a high Ca2+ medium (3.6 mM), the time required to reach the maximum depolarization evoked by PTX was significantly prolonged. In contrast, in a low Ca2+ medium (0.9 mM), PTX caused a marked depolarization soon after application. In a Ca2+-free, Mg2+ (9.0 mM) medium, PTX caused rhythmic oscillatory potentials in both ventral and dorsal roots. 5. The potency of N-acetyl PTX was one hundredth that of the parent compound. 6. It is suggested that PTX may interfere with the stabilizing action of Ca2+ on the neuronal membrane, consequently facilitating Na+ permeability. The primary amine in the PTX molecule may be important for its pharmacological action.