A study of desensitization using voltage clamp

The onset and offset of desensitization produced by carbachol and hexyl and heptyl TMA at voltage-clamped frog endplates were studied. Desensitization onsets exponentially with a rate constant which is proportional to the agonist concentration. The proportionality constant varies with the agonist used. The plateau current finally attained falls steeply to low values with increasing agonist concentration, and with further increase in concentration varies relatively little. The offset of desensitization is sometimes accompanied by the appearance of a second transient increase in current. It is proposed that desensitization is due to channel blockade by the agonist molecule itself.