Defining a region on tetanus toxin responsible for neuromuscular blockade

Administering high doses of tetanus toxin to animals produces neuromuscular blockade. Previous studies, in which specific F(ab) antibody fragments were used to mask the 50,000 MW COOH-terminal portion of the heavy chain (fragment c) on the toxin molecule, have shown that the paralyzing effect of the toxin was most probably located in an area comprising the light chain and the 50,000 MW NH2-terminal portion of the heavy chain (Fragment Ibc). In our study, the toxin was also complexed with F(ab) fragments directed to the light chain (alpha), heavy chain (beta), beta minus IIc, and with monoclonal antibodies to epitopes on IIc and beta minus IIc. Investigating the effect of the resulting complexes both in mice and on the sphincter pupillae muscle in rabbits permitted us to circumscribe further the tetanus toxin neuromuscular blocking activity in a region of the NH2-terminal fragment (Mr = 50,000) of the heavy chain (fragment beta minus IIc). Our results are consistent with the assumption that the beta minus IIc fragment is critical for the neuromuscular blockade activity of tetanus toxin. However, it cannot be ruled out that both the peripheral and central effects of the toxin result from the same portion of the toxin molecule, the nature of the action depending on where the toxin is carried after its introduction into the organism.