Tetrodotoxin

Biosens Bioelectron. 2015 Apr 18;71:256-260.

Development of ELISA and colloidal gold immunoassay for tetrodotoxin detetcion based on monoclonal antibody.[Pubmed: 25913446]

METHODS AND RESULTS:
A monoclonal hybridoma cell named 5B9 against Tetrodotoxin (TTX) was obtained after fusion of myeloma SP2/0 cells with spleen cells isolated from the immunized Balb/c mice. The 5B9 monoclonal antibody (McAb) with high affinity (about 2.55 × 10(9)) is specific to TTX, and this McAb belongs to the immunoglobulin G (IgG) isotype. Finally, an enzyme-linked immunosorbent assay (ELISA) and colloidal gold immunoassay were established based on this McAb. The linear range of ELISA to detect TTX was 5-500 ng/mL, and the limit of detection (LOD) was 4.44 ng/mL. The average CV of intra- and inter-assay was less than 8%, with the samples recovery range of 70.93-99.99%. A competitive format colloidal gold strip was developed for detection of TTX in real samples, and the LOD for TTX is 20 ng/mL, and the assay time of the qualitative test can be finished in less than 10 min without any equipment.
CONCLUSIONS:
The result from test strip revealed that the test strip has a good agreement with those obtained from ELISA.

J Gen Physiol. 1964 May;47:965-74.

TETRODOTOXIN BLOCKAGE OF SODIUM CONDUCTANCE INCREASE IN LOBSTER GIANT AXONS.[Pubmed: 14155438]

Previous studies suggested that Tetrodotoxin, a poison from the puffer fish, blocks conduction of nerve and muscle through its rather selective inhibition of the sodium-carrying mechanism.
METHODS AND RESULTS:
In order to verify this hypothesis, observations have been made of sodium and potassium currents in the lobster giant axons treated with Tetrodotoxin by means of the sucrose-gap voltage-clamp technique. Tetrodotoxin at concentrations of 1 x 10 -7 to 5 x 10 -9 gm/ml blocked the action potential but had no effect on the resting potential. Partial or complete recovery might have occurred on washing with normal medium. The increase in sodium conductance normally occurring upon depolarization was very effectively suppressed when the action potential was blocked after Tetrodotoxin, while the delayed increase in potassium conductance underwent no change.
CONCLUSIONS:
It is concluded that Tetrodotoxin, at very low concentrations, blocks the action potential production through its selective inhibition of the sodium-carrying mechanism while keeping the potassium-carrying mechanism intact.

J Pharmacol Exp Ther. 1998 Mar;284(3):958-65.

Potent modulation of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels by the type II pyrethroid deltamethrin.[Pubmed: 9495855]

METHODS AND RESULTS:
In both Tetrodotoxin-resistant (TTX-R) and Tetrodotoxin-sensitive (TTX-S) sodium channels, deltamethrin greatly prolonged the current during step depolarizing pulse and caused a large and prolonged slow tail current. The activation was shifted by 20 mV in the hyperpolarizing direction. These changes in channel kinetics account for the prolongation of action potential, membrane depolarization and spontaneous discharges in the deltamethrin-treated neurons. The slow tail current of TTX-S sodium channels rose and decayed slowly, showing a hook. By contrast, the slow tail current of TTX-R channels occurred quickly upon step repolarization. The slow tail current in deltamethrin-treated cells developed slowly during a depolarizing pulse, with a time constant in the order of several milliseconds. The percentages of sodium channels modified by deltamethrin were measured as a function of the deltamethrin concentration. The EC50 values were 0.53 microM and 0.37 microM for TTX-S and TTX-R sodium channels, respectively. However, when compared at the level of 5% modification, the potency of deltamethrin for TTX-R channels was 40 to 50 times higher than that for TTX-S channels. Deltamethrin-induced large and prolonged tail current was hardly reversed after prolonged washout with drug-free solution. However, after application of tetramethrin, it was converted into a much shorter tail current. Washout with solution devoid of tetramethrin and deltamethrin resulted in rapid reappearance of the deltamethrin-type tail current.
CONCLUSIONS:
These results suggest that the deltamethrin and tetramethrin share a binding site on the sodium channel and that the slow onset and offset of deltamethrin action are controlled by the rates at which deltamethrin moves and unbinds from the membrane lipid phase rather than by the rate of deltamethrin binding to the sodium channel site.

Org Lett. 2015 Apr 27.

Formal Synthesis of (±)-Tetrodotoxin via the Oxidative Amidation of a Phenol: On the Structure of the Sato Lactone.[Pubmed: 25915710]

A formal total synthesis of (±)-Tetrodotoxin that relies on the bimolecular oxidative amidation of a phenol is described, and a structural correction of the Sato lactone, an important Tetrodotoxin intermediate, is provided. This work lays the foundation for an ultimate enantioselective synthesis.