Voltage-Independent Block of a Neuronal Nicottnic Acetylcholine Receptor by N-Methyl Lycaconitine

Abstract

N-Methyl lycaconitine is the most effective low molecular weight antagonist reported for an insect neuronal nicotinic receptor. In the present study, the citrate salt of this neurotoxin from the plant Delphinium brownii was found to inhibit [3H]-α-bungarotoxin binding to nerve cord extracts of the cockroach Periplaneta americana with a Ki of l.4×10−9moll−1. At a concentration of 1.0×10−7moll−1, N-methyl lycaconitine completely blocked the response to ionophoretically applied acetylcholine recorded from the cell body membrane of the fast coxal depressor motor neurone (Df) in the desheathed metathoracic ganglion of the cockroach. The block was voltage-independent over the range of membrane potential −100 to −30 mV. The effectiveness of N-methyl lycaconitine on the nicotinic receptor, which is present in very high concentrations in the insect nervous system, suggests that this alkaloid is a natural plant protection agent.