Verrucotoxin, a stonefish venom, modulates calcium channel activity in guinea‐pig ventricular myocytes

Background and purpose: Stonefish ( Synanceia genus ) are commonly found in shallow waters of the Pacific and Indian Oceans. The venom of stonefish is stored in the dorsal fine spines and contains a proteinaceous toxin, verrucotoxin (VTX). The stings produced by the spines induce intense pain, respiratory weakness, damage to the cardiovascular system, convulsions and paralysis, sometimes leading to death. Although there are many studies on VTX, the mechanism(s) underlying the VTX‐mediated cardiotoxicity is not yet fully understood. The aim of this study was to investigate the modulation of ion channels in cardiac tissue by VTX. Experimental approach: The effects of VTX on changes in the voltage or current in guinea‐pig ventricular myocytes were investigated using a patch clamp method. Key results: VTX (10 μg ml −1 ) prolonged the action potential duration by 2.5‐fold. VTX increased L‐type Ca 2+ currents ( I Ca(L) ) in a concentration‐dependent manner with a EC 50 value of 7 μg ml −1 and a maximum increase of 3.1‐fold. The non‐selective β‐adrenoceptor antagonist, propranolol (1 μM) and the selective β 1 ‐adrenoceptor antagonist, CGP20712A (10 μM) each abolished the effect of VTX (100 μg ml −1 ) on I Ca(L) . Furthermore, the protein kinase A (PKA) antagonists H‐89 (10 μM) and Rp‐8‐Br‐cAMPS (30 μM) inhibited the effect of VTX on I Ca(L) . Conclusions and implications: VTX modulates Ca 2+ channel activity through the β‐adrenoceptor‐cAMP‐PKA pathway. British Journal of Pharmacology (2007) 151 , 1198–1203; doi: 10.1038/sj.bjp.0707340