Abstract

The effects of histrionicotoxin (HTX) and dihydroisohistrionicotoxin (DHTX) on the depolarization produced by carbamylcholine on the monocellular electroplax preparation of Electrophorus electricus and on binding of [³H]acetylcholine to membrane fragments rich in acetylcholine receptor protein from Torpedo marmorata are described. HTX and DHTX at concentrations of 1.0 µM reversibly and noncompetitively blocked the steady-state depolarization produced by carbamylcholine on the monocellular electroplax preparation. On the other hand, neither HTX or DHTX blocked the binding of [³H]acetylcholine to membrane fragments rich in acetylcholine receptors, even at concentrations of 500 µM. Rather, both toxins increased the affinity of [³H]acetylcholine for the receptor protein in its membrane environment at concentrations which blocked the carbamylcholine effect on the electroplax. The similarity between the effects of histrionicotoxin and those of certain local anesthetics suggests that at the receptor level histrionicotoxin acts as a powerful local anesthetic.