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. 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 voltageclamp technique. Tetrodotoxin at concentrations of 1 X I0 -~ 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. 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.Tetrodotoxin is the active principle of the puffer poison which has long been a matter of interest because the puffer fish is one of the major sea foods in Japan. It blocks peripheral nerve and muscle conduction as well as the central nervous system at very low concentrations (Fleisher, Killos, and
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