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


METHODS
The effects of VTX on changes in the voltage or current in guinea-pig ventricular myocytes were investigated using a patch clamp method.


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
VTX modulates Ca(2+) channel activity through the beta-adrenoceptor-cAMP-PKA pathway.
Yazawa
K
K
Department of Physiology, Graduate School of Medicine and Dental Science, Kagoshima University, 35-1 Sakuragaoka, Kagoshima 890-8544, Japan. yazawak@m3.kufm.kgoshima-u.ac.jp
Wang
J-W
JW
Hao
L-Y
LY
Onoue
Y
Y
Kameyama
M
M
D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005397:Fish Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
D020746:Calcium Channels, L-Type; D005397:Fish Venoms; D006023:Glycoproteins; D011943:Receptors, Adrenergic, beta; C094408:verrucotoxin protein, Synanceia verrucosa; D017868:Cyclic AMP-Dependent Protein Kinases