K+ CHANNEL SUBTYPES IN RAT-BRAIN - CHARACTERISTIC LOCATIONS REVEALED USING BETA-BUNGAROTOXIN, ALPHA-DENDROTOXINS AND DELTA-DENDROTOXINS

Sub-types of fast-activating, voltage-dependent K+ channels were localized in rat brain using the specific probe, alpha-dendrotoxin, in conjunction with the putative K+ channel ligands, delta-dendrotoxin and beta-bungarotoxin. Sheet-film autoradiography of brain sections labelled with radioiodinated delta-dendrotoxin showed that its acceptors occur in most synapse-rich and gray matter regions, and nerve tracts; all of this labelling was abolished by alpha-dendrotoxin or its homologue, toxin I. Other structurally related peptides from mamba snake venom, beta- and gamma-dendrotoxin, were much less effective in preventing delta-dendrotoxin labelling. In common with the sites for alpha-dendrotoxin and beta-bungarotoxin, delta-dendrotoxin acceptors were enriched in cerebral cortex, thalamus and molecular layer of both the cerebellum and dentate gyrus of the hippocampus. However, delta-dendrotoxin failed to show significant binding to the Purkinje cell layer of the cerebellar cortex and stratum lacunosum moleculare of the hippocampal formation, areas labelled prominently by the other two probes. Evidence of this apparent heterogeneity in the toxin-binding proteins was consolidated by the observed inability of delta-dendrotoxin to inhibit I-125-labelled alpha-dendrotoxin or beta-bungarotoxin binding to these specified regions. Thus, delta-dendrotoxin, like beta-bungarotoxin, discriminates between sub-types of alpha-dendrotoxin acceptors but in different fashions. Whilst beta-bungarotoxin interacts preferentially with a sub-population in synaptic areas, delta-dendrotoxin distinguished sub-types in certain synaptic and gray matter regions and, in this, resembles mast cell degranulating peptide, a ligand known to block an alpha-dendrotoxin-sensitive K+ current.