THE MECHANISM UNDERLYING THE CARDIOTOXIC EFFECT OF THE TOXIN FROM THEJELLYFISH CHIRONEX FLECKERI

We have investigated the mechanisms underlying the cardiac effects of the toxin from the box jellyfish Chironex fleckeri. Papillary muscles isolated from the hearts of ferrets and ventricular myocytes isolated from the hearts of ferrets and rats were used. Force, intracellular [C a2+], and membrane potential were monitored in the papillary muscles; contraction, intracellular [Ca2+], intracellular [Na+], and membrane c urrents were monitored in the isolated myocytes. Application of the to xin to these preparations resulted in a large increase in intracellula r [Ca2+] and the adverse symptoms of Ca2+ overload (aftercontractions, spontaneous contractions, a decrease in developed force, and an incre ase in resting force), The response of papillary muscles to the toxin was not inhibited by blockers of Ca2+ or Na+ channels or by inhibitors of the sarcoplasmic reticulum, Na+/K+ ATPase, or Na+/H+ exchange. The response to the toxin was, however, blocked by prior exposure to a so lution which contained no Na+ and by Ni2+. In the isolated myocytes, a s well as an increase in intracellular [Ca2+], the toxin also caused a n increase in intracellular [Na+] and the appearance of a current whic h was inward at negative potentials and reversed at about -10 mV. Thes e data can be explained by the toxin increasing Na+ influx into the ce ll, The increase in intracellular [Na+] will then increase intracellul ar [Ca2+] via the Na+/Ca2+ exchange mechanism, thus producing the obse rved Ca2+ overload. (C) 1995 Academic Press, Inc.