Neurotoxins Distinguish Between Different Neuronal Nicotinic Acetylcholine Receptor Subunit Combinations

Abstract

Neuronal and muscle nicotinic acetylcholine receptor subunit combinations expressed in Xenopus oocytes were tested for sensitivity to various neurotoxins. Extensive blockade of the α3β2 neuronal subunit combination was achieved by 10 n M neuronal bungarotoxin. Partial blockade of the α4β2 neuronal and α1β1γδ muscle subunit combinations was caused by 1,000 n M neuronal bungarotoxin. The α2β2 neuronal subunit combination was insensitive to 1,000 n M neuronal bungarotoxin. Nearly complete blockade of all neuronal subunit combinations resulted from incubation with 2 n M neosurugatoxin, whereas 200 n M neosurugatoxin was required for partial blockade of the α1β1γδ muscle subunit combination. The α2β2 and α3β2 neuronal subunit combinations were partially blocked by 10,000 n M lophotoxin analog‐1, whereas complete blockade of the α4β2 neuronal and α1β1γδ muscle subunit combinations resulted from incubation with this concentration of lophotoxin analog‐1. The α1β1γδ muscle subunit combination was blocked by the α‐conotoxins G 1A and M 1 at concentrations of 100 n M. All of the neuronal subunit combinations were insensitive to 10,000 n M of both α‐conotoxins. Thus, neosurugatoxin and the α‐conotoxins distinguish between muscle and neuronal subunit combinations, whereas neuronal bungarotoxin and lophotoxin analog‐1 distinguish between different neuronal subunit combinations on the basis of differing α subunits.