Verrucotoxin (a venom of stonefish) acts as a β-adrenoceptor agonist in guinea-pig ventricular myocytes

A venomous stonefish (Synanceia verrucosa) is commonly found in shallow waters of the Pacific Ocean and Indian Ocean. Its venom verrucotoxin (VTX) is the protein stored in the dorsal fine spines. The stings produced by the spines induce intensive pain, respiratory weakness, damage of cardiovascular system, convulsions and paralysis leading sometimes to death. Although several studies have been reported, the mechanism of VTX-mediated cardiotoxicity was not fully understood. The aim of this study was to investigate the effects of VTX on ion channels in guinea-pig ventricular myocytes by using the patch clamp method. VTX (10 μg/ml) prolonged action potential duration 2.5-fold. VTX increased L-type Ca2+ current (ICaL) in a dosedependent manner with a half maximum dose of 7 μg/ml and maximally increased ICaL 3.1-fold. VTX decreased the inward rectifier potassium current by 20 %. These effects were completely blocked by a β-adrenoceptor antagonist propranolol (1 μM). These results suggest that the modulation of ion channels by VTX is mediated via β-adrenoceptor stimulation.