Central Action of Dendrotoxin: Selective Reduction of a Transient K Conductance in Hippocampus and Binding to Localized Acceptors

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 83; no. 2; pp. 493 - 497
• Main Authors: Halliwell, James V., Othman, Iekhsan B., Pelchen-Matthews, Annegret, Dolly, J. Oliver
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.01.1986; National Acad Sciences
• Subjects: Animals; Autoradiography; Biological and medical sciences; Cell Membrane - drug effects; Cell physiology; Elapid Venoms - metabolism; Elapid Venoms - pharmacology; Electric Conductivity; Electric current; Electric potential; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Hippocampus; Hippocampus - drug effects; Hippocampus - physiology; In Vitro Techniques; Ion Channels - drug effects; Ion Channels - metabolism; Membrane potential; Membrane Potentials; Membrane Proteins - metabolism; Molecular and cellular biology; Neurons; Neurotransmission; P branes; Pyramidal cells; Rats; Receptors, Drug - metabolism; Steady state current; Toxicity; Toxins; Fixation; Animal; Neurotoxin; Molecular interaction; Ionic current; Inhibition; Mechanism of action; Potassium; Hippocampus; Biological receptor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.83.2.493

Dendrotoxin, a small single-chain protein from the venom of Dendroaspis angusticeps, is highly toxic following intracerebroventricular injection into rats. Voltage-clamp analysis of CA1 neurons in hippocampal slices, treated with tetrodotoxin, revealed that nanomolar concentrations of dendrotoxin reduce selectively a transient, voltage-dependent K conductance. Epileptiform activity known to be induced by dendrotoxin can be attributed to such an action. Membrane currents not affected directly by the toxin include (i) Ca-activated K conductance; (ii) noninactivating voltage-dependent K conductance; (iii) inactivating and noninactivating Ca conductances; (iv) persistent inward (anomalous) rectifier current. Persistence of the effects of the toxin when Cd was included to suppress spontaneous transmitter release indicates a direct action on the neuronal membrane. Using biologically active, 125I-labeled dendrotoxin, protein acceptor sites of high affinity were detected on cerebrocortical synaptosomal membranes and sections of rat brain. In hippocampus, toxin binding was shown autoradiographically to reside in synapserich and white matter regions, with lower levels in cell body layers. This acceptor is implicated in the action of toxin because its affinities for dendrotoxin congeners are proportional to their central neurotoxicites and potencies in reducing the transient, voltage-dependent K conductance.