Nicotinic acetylcholine receptor
Saturation of drug binding sites
Springer Online Journal Archives 1860-2000
Summary 1. To study the quantitative correlation between the stabilizing effect of toxiferine on the postsynaptic membrane and the number of drug binding sites at the motor endplate, experiments were performed on isolated mouse hemidiaphragms using combined electrophysiological and autoradiographic techniques. 2. The membrane stabilizing effect of 14C-toxiferine was investigated over a wide range of concentrations, in order to obtain not only muscle paralysis but the complete abolition of the endplate response to nerve stimulation. 3. Motor endplate activity was recorded intracellularly. For each concentration of the drug the percentage of endplates reacting to nerve stimulation with action potentials (a.p.), or with subliminal endplate potentials (e.p.p.), or being completely blocked, was determined. The mean amplitude of the e.p.p.'s was also calculated. 4. Reduction of the e.p.p. to an undetectable level required a concentration of 14C-toxiferine about 3 times greater than that which induced complete paralysis. 5. Correlation of these data with autoradiographic measurements demonstrated that decreasing e.p.p. amplitude corresponded to increasing values for the number of drug binding sites per endplate. Saturation was reached by that concentration which completely blocked the postsynaptic sensitivity to ACh. 6. It is concluded that at this concentration all the specific drug binding sites are occupied.
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