Abstract

Maitotoxin (MTX), a principal toxin of seafood poisoning, produced powerful cardiotoxic effects on guinea pig isolated left atria at concentrations of 5 X 10(-9) to 3 X 10(-8) g/ml. The MTX-induced increase in resting tension of atria was abolished by Co++, D600 or Ca++-free solution. The tissue Ca content and 45Ca uptake of guinea pig atria were increased by MTX (5 X 10(-9) to 3 X 10(-8) g/ml), and these increases were inhibited markedly by Co++. In isolated rat cardiac myocytes, irreversible contracture was produced by MTX (10(-8) g/ml), and this effect of MTX was suppressed by verapamil or Ca++-free solution. The intracellular free Ca++ concentration of isolated rat myocytes was increased greatly by MTX (10(-9) to 3 X 10(-8) g/ml). Furthermore, the myocardial cells sampled from guinea pig left atria were characterized ultrastructurally by severely overcontracted sarcomeres, swollen mitochondria, peripheral aggregation of nuclear chromatin and loss of granular glycogen, and these morphological changes were abolished by omitting Ca++ from the medium. These results suggest that MTX increases the Ca++ influx through the cardiac muscle membrane to create the Ca-overloaded state and thus caused the cardiotoxic effects.