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

Article Details

Citation

Copy to clipboard

Yazawa K, Wang JW, Hao LY, Onoue Y, Kameyama M

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

Br J Pharmacol. 2007 Aug;151(8):1198-203. Epub 2007 Jun 18.

PubMed ID

17572694 [ View in PubMed

]

Abstract

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 microg 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 microg ml(-1) and a maximum increase of 3.1-fold. The non-selective beta-adrenoceptor antagonist, propranolol (1 microM) and the selective beta(1)-adrenoceptor antagonist, CGP20712A (10 microM) each abolished the effect of VTX (100 microg ml(-1)) on I (Ca(L)). Furthermore, the protein kinase A (PKA) antagonists H-89 (10 microM) and Rp-8-Br-cAMPS (30 microM) inhibited the effect of VTX on I (Ca(L)). CONCLUSIONS AND IMPLICATIONS: VTX modulates Ca(2+) channel activity through the beta-adrenoceptor-cAMP-PKA pathway.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Propranolol	Beta-1 adrenergic receptor	Protein	Humans	Yes	Antagonist	Details