Trypsin inhibits the action of tetrodotoxin on neurones


EVIDENCE suggests that the molecules responsible for membrane excitability are proteins1–4, but they have not been isolated in spite of considerable efforts and their identities remain unknown. Some clues have come from study of the effects of enzymes and group-specific chemicals on appropriate electrophysiological properties of the membrane1–4. In certain nerve and muscle cells the voltage-dependent inward currents which generate action potentials may be carried by Na+ or Ca2+ (refs 5–13). Tetrodotoxin (TTX) specifically blocks the voltage-dependent inward Na+ current in many of these cells14, including neurones of Aplysia10 and Helix11 and is widely used for this reason. It also has the advantage of being a relatively simple molecule of known atomic structure14. But TTX has no effect on Helix neurones when they are isolated from the ganglia in which they are located13. The ganglia are first pretreated with trypsin and we wondered whether the lack of TTX-sensitivity in these preparations was due to some action of this enzyme on the TTX receptor. We have now found that exogenous trypsin modifies the TTX-binding properties of the Na channel without affecting its reversal potential or selectivity against Tris+ and has no measurable effect on the Ca2+ channel. Because trypsin splits polypeptide chains on the carboxyl side of arginine or lysine residues15, it seems likely that the TTX receptor contains either or both of these amino acids but that the selectivity site does not.

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LEE, K., AKAIKE, N. & BROWN, A. Trypsin inhibits the action of tetrodotoxin on neurones. Nature 265, 751–753 (1977).

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