Sodium channel veratridine concentration

Tamplin et. al. (54) observed that V. cholerae and A. hydrophila cell extracts contained substances with TTX-like biological activity in tissue culture assay, counteracting the lethal effect of veratridine on ouabain-treated mouse neuroblastoma cells. Concentrations of TTX-like activity ranged from 5 to 100 ng/L of culture when compared to standard TTX. The same bacterial extracts also displaced radiolabelled STX from rat brain membrane sodium channel receptors and inhibited the compound action potential of frog sciatic nerve. However, the same extracts did not show TTX-like blocking events of sodium current when applied to rat sarcolemmal sodium channels in planar lipid bilayers. 

Current efforts in these studies involve a detailed characterization of pyrethroid-activator interactions and the examination of a broader range of pyrethroids and other compounds as enhancers of activation. Recently, we have found that cismethrin is one of the most effective pyrethroids in this system, producing enhancement at high concentrations equal to or greater than that observed with deltamethrin (Figure 2). The action of cismethrin in the mouse brain system is quite different from its action on neuroblastoma cell sodium channels, where it has no effect on veratridine-dependent activation but is able to antagonize the enhancement produced by other pyrethroids (5). 

We have also defined both the effect of veratridine concentration on sodium channel activation in this system and the impact of , -DDT on the concentration-effect curve for veratridine-dependent activation (Figure 5). Half-maximal activation by veratridine oc-cured at approximately 50 PM, a value very close to that found for the action of this compound in mouse brain synaptosomes (7. , -... 

DDT significantly enhanced veratridine-dependent uptake at all veratridine concentrations above 10 pM, and maximum sodium uptake in the presence of both compounds was achieved at 50 pM, which is the approximate for veratridine alone These findings suggest that , -DDT notuonly enhances veratridine-dependent activation but also increases the potency of veratridine. This result contrasts with the interaction of deltamethrin and veratridine in mouse brain synaptosomes (Figure 1) where the insecticide enhanced activation but did not affect the potency of the activator The only previous report of insecticide-dependent potency shifts in sodium channel activation is in neuroblastoma cells, where pyrethroids increase the potency of batrachotoxin and dihydrograyanotoxin II as sodium channel activators, but do not alter the potency of veratridine (5). These experiments provide the basis for further studies to compare directly the selectivity and sensitivity of sodium channels from mammalian and fish brain in their interactions with insecticides ... 

Amar M, Pichon Y, Inoue I (1991) Micromolar concentrations of veratridine activate sodium channels in embryonic cockroach neurones in culture. Pflugers Arch 417 500-508... 

Based on the ability of PSP toxins to block sodium channels, a reverse toxicological assay has been proposed using cultured cerebellar neurons in which protection by saxitoxins from neurodegeneration induced by the sodium channel activator veratridine is measured. PSP content is calculated by comparison with known concentrations of purified saxitoxin, and values obtained with this method show very good correlation with values from LC and mouse bioassay. 

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