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Journal of Experimental Biology 118,37-52 (1985)
Published by Company of Biologists 1985

Nereistoxin: Actions on a CNS Acetylcholine Receptor/Ion Channel in the Cockroach Periplaneta Americana

D. B. SATTELLE ¹, I. D. HARROW ², J. A. DAVID ¹, M. PELHATE ³, J. J. CALLEC ⁴, J. I. GEPNER ⁵, and L. M. HALL ⁶

¹ A.F.R.C. Unit of Insect Neurophysiology and Pharmacology, Department of Zoology, Downing Street, Cambridge CB2 3EJ, U.K.
² A.F.R.C. Unit of Insect Neurophysiology and Pharmacology, Department of Zoology, Downing Street, Cambridge CB2 3EJ, U.K.; Animal Health Biology Department, Pfizer Central Research, Sandwich, Kent, CT13 9NJ. U.K.
³ A.F.R.C. Unit of Insect Neurophysiology and Pharmacology, Department of Zoology, Downing Street, Cambridge CB2 3EJ, U.K.; Faculté de Médeciné, Université d'Angers, rue Haute de Reculée, Angers, 49045, France
⁴ A.F.R.C. Unit of Insect Neurophysiology and Pharmacology, Department of Zoology, Downing Street, Cambridge CB2 3EJ, U.K.; U.E.R. Sciences Biologiques, Université de Rennes, Rennes, France
⁵ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, U.S.A.
⁶ Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, NY 10461, U.S.A.

Nereistoxin hydrogen oxalate (NTX), at low concentrations (in the range 2.0x10^-8-10 x 10^-6moll^-1), induced a dose-dependent partial block of transmission at cereal afferent, giant interneurone synapses in the terminal abdominal ganglion (A6) of the cockroach Periplaneta americana which was not accompanied by changes in either membrane potential or input resistance of the postsynaptic membrane. At a concentration of 1.0 x 10^-7 moll^-1, NTX suppressed, in a voltage-dependent manner, acetylcholine-induced currents recorded from voltage-clamped cell bodies of both giant interneurone 2 (GI2) in A6, and the fast coxal depressor motoneurone of the metathoracic ganglion (T3). At higher concentrations (in the range 1.0 x 10^-5-1.0 x 10^-3moll^-1) depolarization of the postsynaptic membrane was observed. Axonal depolarization was noted at concentrations above 1.0 x 10^-4moll^-1. Voltage-clamp experiments showed that the axonal actions of NTX included suppression of sodium and potassium currents and an increase in the membrane leak current. The concentrations of NTX (in the range 1.0 x 10^-5-1.0 x 10^-3 moll^-1) which show the postsynaptic depolarizing effect are in the same range as the NTX concentrations (l.7 x l0^-4 and 6.6 x 10^-5moll^-1) required for 50% inhibition of the binding of ¹²⁵I--bungarotoxin to Periplaneta abdominal nerve cord extracts and Drosophila head extracts, respectively. Thus a potent, voltage-dependent, blocking action of NTX is detected at the CNS acetylcholine receptor/ion channel complex of the cockroach. This, possibly together with the synaptic and axonal depolarizing effects noted at much higher concentrations, may contribute to the mechanism of action of this natural invertebrate neurotoxin which is also the active form of the synthetic insecticide Cartap.

Key words: Nereistoxin, acetylcholine receptor/ion channel, Periplaneta americana CNS, Drosophila melanogaster

Accepted on April 2, 1985