stonefish - genus : Scorpaenidae, ~~sometimes Synanceia, name: Synanceia horrida [ Hollow-cheek stonefish ] , / Estuarine stonefish, --- "conus" genus/speices of shellfish-thingy.
Stonefish (Synanceia genus) Venom possible mechanisms of action: --
- verrucotoxin (VTX) - 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.
- verrucotoxin (VTX) inhibits ATP-sensitive K+ (KATP) current (K+ = potassium). Pinacidil, a KATP channel opener, induces a KATP current, which is suppressed by VTX "with a half maximum concentration of 16.3 microg/ml". This inhibitory effect on KATP currents was suppresed by atropine (1 microM), or by 4-diphenylacetoxy-N-methylpiperidine (100 nM)-[which is apparently a M3 receptor antagonist]. Also, the effect of verrucotoxin on KATP current was attenuated by the protein kinase C (PKC) inhibitor chelerythrine (10 microM) and calphostin C (10 microM), but notItalic text by the cAMP-dependent protein kinase (PKA) inhibitor H-89 (0.5 microM). "These results suggest that verrucotoxin inhibits KATP current through the muscarinic M3 receptor-PKC pathway."
link/reference - [1]
the venom different members of the synaceia genus may possess different mechanisms of action, thus , when possible, the specific member will be specified
- Synanceia verrucosa - [ Reef stonefish ] -
(quote) "Verrucotoxin is the major component of venom from the stonefish (Synanceia verrucosa). Stings from the dorsal spines of the stonefish produce intensive pain, convulsions, hypotension, paralysis, respiratory weakness and collapse of the cardiovascular system, occasionally leading to death. It has been reported that verrucotoxin might modulate ATP-sensitive K+ (KATP) current in frog atrial fibers. However, the mechanism by which verrucotoxin acts on KATP current remains unclear. In this study, we examined whether verrucotoxin inhibited KATP current in guinea pig ventricular myocytes, using the patch clamp method. Verrucotoxin suppressed KATP current induced by pinacidil (KATP channel opener) in a concentration-dependent manner, with a half maximum concentration of 16.3 microg/ml. The effect of verrucotoxin on KATP current was suppressed by atropine (1 microM), a muscarinic receptor antagonist, or by 4-diphenylacetoxy-N-methylpiperidine (100 nM), a muscarinic M3 receptor antagonist. Furthermore, the effect of verrucotoxin on KATP current was attenuated by the protein kinase C (PKC) inhibitor chelerythrine (10 microM) and calphostin C (10 microM), yet not by the cAMP-dependent protein kinase (PKA) inhibitor H-89 (0.5 microM). These results suggest that verrucotoxin inhibits KATP current through the muscarinic M3 receptor-PKC pathway. These findings enhance our understanding of the toxic effects of verrucotoxin from the stonefish."
- [2]
quote - " Experimentation is difficult due to venom instability. Activity is lost by distilled water, lyophilisation in buffers, several successive freezing and defreezing. In addition, when venom is broken, other pharmacological effects are evidenced, for instance, with Synanceia verrucosa venom, hypertensive phase takes the place of hypotension. It is difficult to distinguish toxin effect from this of denaturation products of the toxin. "
"Norepinephrine is present in Synanceia venom, and it seems that acetylcholine exists in some venom, at least when diluted in saline solution. Other biological active products are present."
- "Stonustoxin from Synanceia horrida exerts its action through NO-synthase ( Nitric oxide synthase liberation, and its primary action can be attributed to its potent vasorelaxant activity, causing a rapid, marked and irreversible hypotension."
- this implies that highly increased activity of Nitric Oxide could be responsible for a portion of the effects of Stonefish envenomation. Nitric Oxide, when activity increases above normal levels, becomes exceedingly dangerous, and produces free radicals and oxidative stress by reacting with stuff such as the superoxide anion.
- the increas of Nitric Oxide Synthase, and subsequent Nitric Oxide activity, could be caused by the VTX's amplification of L-type Ca(2+) channel activity, which it accomplishes presumably through the beta-adrenoceptor-cAMP-PKA pathway.
image : 
http://upload.wikimedia.org/wikipedia/commons/a/ab/Synanceia_horrida_Day.png
Venom mechanism of action -
- "The effects of trachynilysin (TLY), a protein toxin isolated from stonefish (Synanceia trachynis) venom, were studied on the electrical and mechanical activities of frog atrial fibres. TLY (1 microg/ml) hyperpolarized the membrane, shortened the action potential (AP) duration (APD), exerted a negative inotropic effect and elicited contracture. These effects did not develop in the presence of atropine. TLY shortened the APD of fibres isolated from a frog completely paralyzed with botulinum type A toxin, in the presence of Ca2+ but not when Ca2+ was replaced by Sr2+. TLY increased the basal and the peak of the fluorescence ratio of stimulated fibres loaded with fura-2. Confocal laser scanning microscopy revealed the existence of a diffuse innervation in atrial tissue. Our results suggest that TLY enhances the release of acetylcholine from atrial cholinergic nerve terminals and activates indirectly muscarinic receptors leading to a shortening of APD. They also show that the mechanical effects induced by TLY are due to an increase of the Ca2+ influx and to a rise in intracellular Ca2+ levels which leads to (i) a slowing of the Na+/Ca2+ exchange activity, which accounts for the contracture and (ii) the activation of a Ca2+-dependent K+ current involved in the APD shortening."
http://www.ionchannels.org/showabstract.php?pmid=8470134
- " Our results indicate that the ability of stonefish venom to elicit spontaneous quantal acetylcholine release from vertebrate motor nerve terminals is a function of trachynilysin, which selectively stimulates the release of small clear synaptic vesicles and impairs the recycling of small clear synaptic vesicles but does not affect the release of large dense-core vesicles. Trachynilysin may be a valuable tool for use in other secretory terminals to discriminate between neurotransmitter and neuropeptide release. "
Trachynilysin mediates SNARE-dependent release of catecholamines from chromaffin cells via external and stored Ca2+.
Meunier FA, Mattei C, Chameau P, Lawrence G, Colasante C, Kreger AS, Dolly JO, Molgó J.
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AY, UK.
Abstract Trachynilysin, a 159 kDa dimeric protein purified from stonefish (Synanceia trachynis) venom, dramatically increases spontaneous quantal transmitter release at the frog neuromuscular junction, depleting small clear synaptic vesicles, whilst not affecting large dense core vesicles. The basis of this insensitivity of large dense core vesicles exocytosis was examined using a fluorimetric assay to determine whether the toxin could elicit catecholamine release from bovine chromaffin cells. Unlike the case of the motor nerve endings, nanomolar concentrations of trachynilysin evoked sustained Soluble N-ethylmaleimide-sensitive fusion protein Attachment Protein REceptor-dependent exocytosis of large dense core vesicles, but only in the presence of extracellular Ca2+. However, this response to trachynilysin does not rely on Ca2+ influx through voltage-activated Ca2+ channels because the secretion was only slightly affected by blockers of L, N and P/Q types. Instead, trachynilysin elicited a localized increase in intracellular fluorescence monitored with fluo-3/AM, that precisely co-localized with the increase of fluorescence resulting from caffeine-induced release of Ca2+ from intracellular stores. Moreover, depletion of the latter stores inhibited trachynilysin-induced exocytosis. Thus, the observed requirement of external Ca2+ for stimulation of large dense core vesicles exocytosis from chromaffin cells implicates plasma membrane channels that signal efflux of Ca2+ from intracellular stores. This study also suggests that the bases of exocytosis of large dense core vesicles from motor nerve terminals and neuroendocrine cells are distinct. - [3]
Stonefish Images - [4]
images of other similar-looking fishes - [5]
more info on local venemous/dangerous marine animals: [6]
![[6]](http://www.google.com/imgres?imgurl=http://www.mondomaldive.com/Fish/Image_Fish/synanceia-verrucosa.jpg&imgrefurl=http://www.mondomaldive.com/fish_dangerous.html&usg=__o1LRGKub4bFOmPLd6TjG2Qkyg3o=&h=155&w=283&sz=12&hl=en&start=6&zoom=1&tbnid=1xNmSwsmAU26MM:&tbnh=62&tbnw=114&prev=/images%3Fq%3DSynanceia%26um%3D1%26hl%3Den%26sa%3DN%26tbs%3Disch:1&um=1&itbs=1){kind=link}
jellyfish,
venom affects NMDA, Calcium, Sodium, Potassium, Chloride channels, also Acetylcholine and Adrenergic and Substance P/Neurokinin,
possible antidotes include: (various subtypes) of sodium channel blockers/calcium channel blockers, NMDA/Ampa/Kainate receptor antagonists, glutamate/aspartate release inhibitors, substance P antagonists??, antimuscarinics......... however most Venoms possess anti-nicotinic activity so only selective Muscarinic antagonists should be used in low doses, preferably not at all due to additive negative effects upon symptoms of poisonoing.