CARDIOTOXIC ACTIONS OF STHICHOLYSINS I AND II, TWO CYTOLYSINS ISOLATED FROM THE SEA ANEMONE Stichodactyla helianthus

Summary The sthicholysins I y II, are cytolytic proteins from the sea anemone Stichodactyla helianthus that interact with biologic membranes and form an oligomeric pore and thus produce the cellular lysis. In general the cytolysins are very lethal in mammals. The cardiotoxic activity of the cytolysins seems to be the most important effect that lead animals to death, so our purpose was to study the actions of sthicholysins I and II on action potential and contraction of isolated perfusing rat heart (Langendorff) and rat ventricular papillary muscle and on the sodium and calcium currents of isolated rat ventricular cardiomyocytes using the patch-clamp technique in whole cell variant. Also we characterized a possible pharmacologic action of theses cytolysins, additional and independent of the forming pore activity, analysing all the experiments mentioned here, but incubating the cytolysins in a basic pH (pH=11.5), because at this pH value these proteins lost the cytolytic action. Both cytolysins produced a powerful cardiotoxic action, characterized by bradycardia and depressed contraction. Also they produced arrhythmias and death of the preparations. Both compounds depressed the sodium current and without effect on calcium current and they produced the cellular death. All effects were irreversibles. When the cytolysins were preincubated to pH = 11.5, also they produced bradycardia and depressed the contraction of perfusing isolated rat hearts (Langendorff), but less powerful and the preparations did not die. However, the cytolysins had not effects on sodium and calcium currents and they did not produced cellular death. These results suggest that the additional pharmacologic action seen in Langendorff experiments is not linked with these ionic channels.