Blockade of acetylcholine receptors by cobra toxin: electrophysiological studies

Microelectrode techniques were used to investigate the manner in which a pure polypeptide toxin from cobra venom blocks transmission at the frog myoneural junction. At concentrations of 16-114 nM, the toxin causes an irreversible exponential decline in the amplitude of the end plate potential as a result of a decrease in the sensitivity of the postsynaptic receptors for acetylcholine. Other processes, such as spontaneous and impulse-evoked acetylcholine release, acetylcholinesterase activity, and passive electrical properties of the muscle fiber membrane, remain unaffected. The rate constant for inactivation of receptors increases linearly with toxin concentration. The constant of proportionality probably describes the binding of toxin to the receptor and equals 1.5 x 10⁵ M⁻¹ sec⁻¹. Certain complications in these experiments arise because diffusion barriers limit the access of toxin molecules to the receptors.