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Cytotoxic actions of palytoxin on aortic smooth muscle cells in culture
Author(s) -
Sheridan Robert E.,
Deshpande Sharad S.,
Adler Michael
Publication year - 2005
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1080
Subject(s) - palytoxin , vascular smooth muscle , ouabain , verapamil , depolarization , amiloride , pharmacology , biology , extracellular , myocyte , medicine , calcium , chemistry , endocrinology , biochemistry , toxin , sodium , organic chemistry , smooth muscle
Palytoxin (PTX), isolated from a zoanthid of the genus Palythoa , is the most potent marine toxin known. Intoxication by PTX leads to vasoconstriction, hemorrhage, ataxia, muscle weakness, ventricular fibrillation, pulmonary hypertension, ischemia and death. In this study, clonal A7r5 rat aortic smooth muscle cells were used to study the mechanism of PTX‐mediated cytotoxicity. A7r5 cells exposed to PTX for ≥ 15 min exhibited surface granularities, vacuoles and rounding. These alterations culminated in a loss of viability as indicated by marked increases in the release of lactate dehydrogenase. Electrophysiological recording from A7r5 cells disclosed a profound membrane depolarization and an increase in conductance to Na + and K + . PTX‐mediated cytotoxicity could not be reversed by washout or by the addition of 10 µ m verapamil but was antagonized by 100 µ m ouabain or by removal of extracellular Na + or Ca 2+ . In light of the involvement of vascular smooth muscle in PTX poisoning, A7r5 cells could serve as a useful model to test specific drugs for treatment of PTX intoxication. Copyright © 2005 John Wiley & Sons, Ltd.