Histrionicotoxin enhances agonist-induced desensitization of acetylcholine receptor.

Dihydroisohistrionicotoxin inhibits acetylcholine receptor-dependent 22Na+ uptake of cultured chick muscle cells with a KI of 0.2 micrometer. The inhibition is noncompetitive with respect to agonists. The toxin enhances desensitization of the receptor by agonists which is accompanied by a 10-fold increase in receptor affinity for agonists. Dihydroisohistrionicotoxin increases the affinity of the desensitized form of the receptor for agonists but not antagonists. The results suggest that dihydroisohistrionicotoxin inhibits the acetylcholine receptor by causing an increase in the affinity of the desensitized form of the receptor for agonists and thereby stabilizing the desensitized state.