KINETIC-STUDIES ON THE INTERACTION BETWEEN BOTULINUM TOXIN TYPE-A AND THE CHOLINERGIC NEUROMUSCULAR-JUNCTION

  • 1 January 1980
    • journal article
    • research article
    • Vol. 212  (1) , 16-21
Abstract
Botulinum toxin-induced paralysis of neuromuscular transmission, as studied in the rat nerve-diaphragm, involves at least 3 steps. There is an initial binding step that is nontoxic, a translocation step that is nontoxic and a subsequent lytic step that produces blockade of transmission. In the absence of nerve stimulation, the binding step has a half-time of .apprx. 12 min and a rate constant of .apprx. 0.058/min. The binding step does not require Ca2+ or nerve stimulation, and it has a low temperature dependence (Q10 [rate increase due to 10.degree. C increase] .apprx. 1.6). In the absence of nerve stimulation, the translocation step has a half-time of .apprx. 4.9 min and a rate constant of .apprx. 0.141/min. Translocation requires physiological concentrations of Ca. In the virtual absence of nerve stimulation (1 .times. 10-2 Hz), the lytic step has a half-time of .apprx. 55 min and a rate constant of .apprx. 0.013 .cntdot. min. The lytic step requires Ca, is facilitated by nerve stimulation and has a high temperature dependence (Q10 .apprx. 4.2). A model for botulinum toxin interaction with the cholinergic nerve terminal is proposed.

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