title: Verrucotoxin, a stonefish venom, modulates calcium channel activity in guinea-pig ventricular myocytes.
abstract: 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.
authors.affiliation: 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
authors.forename: K
authors.initials: K
authors.lastname: Yazawa
authors.forename: J-W
authors.initials: JW
authors.lastname: Wang
authors.forename: L-Y
authors.initials: LY
authors.lastname: Hao
authors.forename: Y
authors.initials: Y
authors.lastname: Onoue
authors.forename: M
authors.initials: M
authors.lastname: Kameyama
mesh_terms: 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
chemical_list: 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