Effect of palytoxin on membrane and potential and current of frog myelinated fibers

Abstract

Palytoxin is a highly toxic compound isolated form several zoanthid Palythoa species. The effects of palytoxin on the nodal membrane of frog myelinated fiber have been studied under current clamp and under voltage clamp conditions. Under current clamp conditions, palytoxin (0.1 microng/ml, 3 x 10(-8)M) induces a depolarization which is not reversed by washing. The resting potential reaches a value of -35 mV after 10 minutes. During the same period, the evoked action potential shows a gradual decline and finally disapears after about 30 minutes. The membrane depolarization is suppressed by removal of Na ions from the external medium, but only slightly diminished when tetrodotoxin (10(-6)M) is subsequently added to the external medium. When the potential of the nodal membrane is maintained at -70 mV, palytoxin (0.1 microng/ml) causes the appearance of an inward current that increases in magnitude during 30 minutes before attaining a steady-state value. The kinetics of development of that current is modified in the presence of tetrodotoxin or saxitoxin. Voltage clamp analysis shows that palytoxin causes an increase of the resting sodium permeability that is accompanied by a shift of the voltage dependence of the transient sodium permeability in the direction of membrane hyperpolarization. The shift in the voltage dependence of the transient permeability is accompanied by a decrease of the peak transient permeability. A similar shift in the potential dependence of the sodium inactivation is observed. During and after the application of palytoxin, the internal sodium concentration increases. The steady-state (potassium) conductance is also decreased at the same time as the leak current is increasing.