Abstract
Verrucotoxin (VTX) is the major component of venom from a stonefish (Synanceia Verrucosa). Stings of the dorsal spines of the stonefish produce intensive pain, convulsions, hypotension, paralysis, respiratory weakness and collapse of the cardiovascular system leading sometimes to death. It is reported that VTX might modulate ATP-sensitive K+ (KATP) current in frog atrial fibres. However, the mechanism by which VTX acts on KATP current remains unclear. In this study, we examined whether VTX could inhibit KATP current in guinea-pig ventricular myocytes by the patch clamp method. VTX suppressed KATP current induced by pinacidil (a KATP channel opener) in a dose-dependent manner with a half maximum dose of 16.3 μg/ml. The effect of VTX on KATP current was suppressed by atropine (1 μM), a muscarinic receptor antagonist or 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, 100 nM), a M3 muscarinic receptor antagonist. Moreover the effect of VTX on KATP current was attenuated by a PKC inhibitor chelerythrine (10 μM) but not by a PKA inhibitor H-89 (0.5 μM). These results suggest that VTX inhibits KATP current through the M3 receptor- PKC pathway. [Jpn J Physiol 55 Suppl:S131 (2005)]
