cymarine and palytoxin

We examined the properties of the current induced by palytoxin in single ventricular cells of rats. The current was measured by a whole cell voltage clamp method. When the cell was held at -75 mV, palytoxin induced a sustained inward current in a concentration-dependent manner (2-100 pmol/l). The time-course of the inward current paralleled that of the depolarization. At a holding potential of +50 mV, it caused an outward current. Palytoxin-induced current reversed at 0 mV and its current-voltage relation was almost linear at either negative or positive voltage. Substitution of external NaCl with choline-Cl suppressed the palytoxin-induced inward current but not the outward current, by shifting the reversal potential to levels more negative than -50 mV. A cardiac glycoside, cymarin (10 and 100 mumol/l) partially inhibited the palytoxin-induced current without changing the reversal potential, only when applied before palytoxin. Palytoxin decreased the nicardipine-sensitive Ca2+ current. These data suggest that palytoxin-induced inward current is carried by extracellular Na+ and the outward current is carried mainly by intracellular K+, and that the inward current is responsible for the toxin's depolarizing action. The antagonism by cysmarin indicates that the site of action of palytoxin is in the vicinity of the binding site of cardiac glycosides.

Topics: Acrylamides; Animals; Calcium; Calcium Channels; Cnidarian Venoms; Cymarine; Female; Heart; Heart Ventricles; In Vitro Techniques; Ion Channels; Male; Membrane Potentials; Perfusion; Rats; Sodium