Convulsant and Possible Anticholinergic Actions of Dendrotoxin in the Amphibian Spinal Cord

Abstract

1 Dendrotoxin (DTOX)6, 6a and 5,6-1, fractions of the venom isolated from the green mamba (Dendroaspis viridis) promoted both spontaneous and stimulus-coupled rhythmic activity and antagonized the cholinergically mediated ventral root-dorsal root potential (VR-DRP) of frog spinal cord. The different time course and reversibility of these two effects indicates that the toxin has two entirely separate sites of action on the frog spinal cord. 2 Since DTOX 6 neither blocked nor enhanced responses of ventral and dorsal roots to glutamate, -y-aminobutyric acid (GABA), ,3-alanine, glycine or aspartate, it is unlikely that its convulsant action resulted from an alteration of the postsynaptic actions of inhibitory or excitatory amino acids. 3 An alteration in the threshold for action potential generation could perhaps contribute to the convulsant action of DTOX 6, although other mechanisms such as blockade of the release of unspecified inhibitory substances cannot be excluded. 4 In addition to the lack of effect on amino acid responses, DTOX failed to block the polysynaptic DR-VRP or DR-DRP pathways, which are mediated at least in part by amino acid neurotransmitters. Although this would be consistent with a specific action of DTOX at the cholinergic synapse of the VR-DRP pathway, this site of action has not yet been demonstrated unequivocally. Other possible mechanisms whereby DTOX could block VR-DRP are discussed.

Energetic and structural interactions between δ-dendrotoxin and a voltage-gated potassium channel 1 1Edited by G. von Heijne

“…These toxins have been used to probe the function and biochemical composition of K channels in the central nervous system (Parcej & Dolly, 1989;Rehm & Lazdunski, 1988;Benishin et al, 1988). Toxin administration prevents repolarization of presynaptic terminals and leads to uncontrolled neurotransmitter release and seizure activity (Anderson, 1985;Bagust et al, 1997;Black et al, 1986;Collier et al, 1981;Halliwell et al, 1986;Harvey & Gage, 1981;Harvey & Anderson, 1985;Silveira et al, 1988a,b;Velluti et al, 1987).…”