Stonefish (Synancea verrucosa, Bloch & Schneider, 1801) is one of the deadliest fish in the world. Verrucotoxin is the main ingredient of the stonefish venom. A sting of the dorsal spine causes intensive pain, convulsions, paralysis, hypotension, respiratory distress, collapse of a cardiovascular system, and often can have a deadly outcome. It has been reported that verrucotoxin can modulate Ca2+ channels and ATP-sensitive K+(KATP)channels in frog atrial fibers inducing hypotension, and also it has hemolytic activity. However, the cellular and molecular mechanisms of verrucotoxin toxicity, especially its cardiotoxicity towards the mammalian heart, have not yet been fully investigated. The results suggest that verrucotoxin inhibits KATP channels through the muscarinic M3 receptor pathway. These findings allow us a better understanding of the toxic effects of verrucotoxin from stonefish.