Effects of alpha-dendrotoxin and dendrotoxin K on extracellular excitatory amino acids and on electroencephalograph spectral power in the hippocampus of anaesthetised rats.
Dendrotoxins, important pharmacological tools for studying K(+) channels, are potently convulsant in the central nervous system and evidence suggests that different members of the dendrotoxin family may act at pre- or post-synaptic sites. Using a combination of intrahippocampal infusion, microdialysis and electroencephalograph (EEG) recording, we have compared the effects of alpha-dendrotoxin and dendrotoxin K on extracellular levels of excitatory amino acids in anaesthetised rats. Our findings show that although infusion of 35 pmol of both peptides was associated with elevated extracellular aspartate and glutamate, these increased levels were more sustained with dendrotoxin K. Furthermore, there was EEG evidence of an associated transient functional change consistent with an action on pre-synaptic K(+) channels. In contrast, infusion of alpha-dendrotoxin produced only a brief effect on amino acid levels and no evidence of a functional consequence.
Richards
D A
DA
Department of Pharmacology, Division of Neuroscience, School of Medicine, University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK. d.a.richards@bham.ac.uk
Morrone
L A
LA
Bagetta
G
G
Bowery
N G
NG
D000758:Anesthesia; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004546:Elapid Venoms / Q000008:administration & dosage*; D004569:Electroencephalography / Q000187:drug effects; D018846:Excitatory Amino Acids / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D010455:Peptides / Q000008:administration & dosage*; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004546:Elapid Venoms; D018846:Excitatory Amino Acids; D010455:Peptides; D015221:Potassium Channels; C081506:dendrotoxin K; D001224:Aspartic Acid; D018698:Glutamic Acid; C020273:dendrotoxin