Mechanism of the cardiotoxic action of palytoxin.
Palytoxin (PTX) is a non-12-O-tetradecanoylphorbol-13-acetate-type tumor promoter that has potent cardiotoxic properties. In embryonic chick ventricular cells, PTX increased [Ca2+]i (K0.5 = 5 nM) in a manner that was dependent on the presence of extracellular Ca2+. The action of PTX was not consequent to its depolarizing action, to the opening of voltage-dependent Ca2+ channels, to an intracellular Na+ load, or to intracellular acidification. Flow cytometric analysis of the [Ca2+]i distribution in PTX-treated cells showed that only the largest ventricular cells responded to the toxin. All ventricular cells responded to PTX by intracellar acidification. PTX also increased 22Na+ uptake by cardiac cells (K0.5 = 100 nM) via a pathway that was sensitive to 3,4-dichlorobenzamil (K0.5 = 8 microM), suggesting a possible involvement of the Na+/Ca2+ antiporter. We conclude that the action of PTX in chick cardiac cells is distinct from that in erythrocytes or in fibroblasts and that it likely involves several distinct mechanisms. A primary action of PTX could be to open a Ca2+ uptake pathway in the plasma membrane, which would then trigger 22Na+ uptake by the Na+/Ca2+ antiporter.
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Institut de Pharmacologie Moléculaire et Cellulaire, UPR 411 CNRS, Valbonne, France.
Vigne
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Breittmayer
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D000178:Acrylamides; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002642:Chick Embryo; D003064:Cnidarian Venoms / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D000095702:Polyether Toxins
D000178:Acrylamides; D002118:Calcium; D003064:Cnidarian Venoms; D011188:Potassium; D012964:Sodium; C010272:palytoxin; D000095702:Polyether Toxins