The neural effects of palytoxinThe neural effects of palytoxin

Palytoxin, the most potent known marine toxin, has been demonstrated to produce acute neurological disturbances in several animal species and, possibly, even in humans. However, the effects of palytoxin on excitable membranes have not been well characterised or explained. Palytoxin occurs within the same ecosystem in which other seafood toxins such as ciguatoxin, saxitoxin and brevetoxins are found. Also, several reports suggest that, occasionally, palytoxin may contribute to the ciguatera syndrome. As these other toxins are known to affect the sodium ion channel, either by activation or inactivation, evidence that palytoxin may also affect this structure was sought. The studies performed on the ventral coccygeal nerve of the rat tail, subsequent to an intraperitoneal injection of palytoxin, demonstrated a significant slowing of mixed nerve and motor conduction velocities and a reduction in the amplitude of the mixed nerve and motor action potentials. However, palytoxin exerted no effect on the latency of the shortest F-wave response. In the palytoxin-treated group, the absolute and relative refractory periods were prolonged. Palytoxin also appeared to induce a significant prolongation of the supernormal period of nerve excitability. The response of the palytoxin-treated ventral coccygeal nerve to repetitive stimulation demonstrated no consistent abnormality. These studies lend indirect support to the proposition that at least one action of palytoxin is that of an alteration in the excitability of neural tissue by inducing persistent sodium ion channel activation. Lignocaine, administered via the intraperitoneal route, was demonstrated to reverse many of the electrophysiological disturbances and, particularly, the prolonged supernormal period, in palytoxin-treated rats. These results suggest that prior activation of sodium ion channels by palytoxin may be blocked by lignocaine. Ethanol, administered via the intraperitoneal route, was observed to reverse many of the electrophysiological disturbances recorded in the palytoxin-treated rats, however, the supernormal period remained prolonged, yet not particularly enhanced or diminished in magnitude. Ouabain, administered via the intraperitoneal route, also reversed many of the electrophysiological disturbances induced in palytoxin-treated rats. However, in these animals, the palytoxin-induced supernormal period remained prolonged, yet not exaggerated or diminished in magnitude. These results suggest that membrane excitability may occur independently of, or with, the (Na+,K+)A TPase mechanism. The effect of palytoxin on mammalian nerve tissue appeared to be modified at a lower temperature. Mixed nerve and motor conduction, F-wave responses, absolute and relative refractory period and supernormal period studies were performed on palytoxin-treated animals at 25°C. The only significant abnormalities were a prolongation of the relative refractory period and of the supernormal period. This study suggests that, at least, in mammalian nerve tissue, this toxin is less active at a lower ambient temperature. In terms of central studies, in palytoxin-treated rats the brainstem auditory evoked response was not significantly altered although there was significant prolongation of the corticospinal evoked response. This finding suggests that palytoxin is capable of crossing the blood-brain barrier and, then, exerting an effect on central nerve membranes. These results are similar to those induced by ciguatoxin in the ventral coccygeal nerve of the rat. Both toxins produce slowing of the mixed nerve and motor conduction velocities, a reduction in the amplitude of the mixed nerve and motor action potentials and a prolongation of the refractory period and supernormal period. Lignocaine abolishes the supernormal period induced by both toxins. At a temperature of 25°C, both toxins produce reduced electrophysiological effects, in comparison with those produced at 37°C. Ciguatoxin is known to bind to and to activate or open sodium ion channels. These studies suggest that at least one action of palytoxin may be that of a similar activation of sodium ion channels. With reference to these studies and to the fact that both toxins occur within the same ecosystem, palytoxin could potentially contribute, on occasions, to the ciguatera syndrome