Studies on the mechanism of the positive inotropic effect of ATX II (Anemonia sulcata) on isolated guinea pig atria.
The basic polypeptide ATX II (MW 4,770) isolated from the sea anemone Anemonia sulcata evokes a pronounced and dose-dependent positive inotropic effect in different mammalian heart preparations. The mechanism of this effect is so far unknown. (a) Investigations on isolated guinea pig atria indicate that changes of the steady state cellular Na, K and Ca concentrations cannot account for the positive inotropic effect. (b) An increase of the surface pressure of phospholipid monolayers was observed only at cardiotoxic ATX II concentrations. However, the 45Ca binding to phosphatidylserine, as the essential Ca-binding phospholipid, was not changed even at cardiotoxic ATX II concentrations. (c) Neither the enzymatic activity nor the ouabain inhibition kinetic of an isolated Na/K-ATPase preparation was affected by ATX II. (d) In intact electrically stimulated (1 Hz) guinea pig atria the binding of [3H]ouabain increases by about 50% at a positive inotropic ATX II concentration. The results suggest that the positive inotropic effect of ATX II is not caused by an unspecific membrane damaging action or by a direct interaction with the Na/K-ATPase. The increased binding of [3H]ouabain to intact heart muscles indirectly reflects an increased pump activity of the Na/K-ATPase, which is caused by an elevated Na transient due to the electrophysiologically well-established mechanism of the ATX II action on fast Na channel, i.e., delayed inactivation of the fast Na flux. However, the exact mechanism of the ATX II induced positive inotropic effect remains unknown.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003063:Cnidaria; D003064:Cnidarian Venoms / Q000494:pharmacology*; D004573:Electrolytes / Q000032:analysis; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000032:analysis / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D010042:Ouabain / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D012615:Sea Anemones; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical
D003064:Cnidarian Venoms; D004573:Electrolytes; D009498:Neurotoxins; D010743:Phospholipids; D010042:Ouabain; C028800:toxin II (Anemonia sulcata); D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium