Heterogeneous competition of Kv1 channel toxins with kaliotoxin for binding in rat brain: autoradiographic analysis.
The alpha-subunits of Kv1 channels display characteristic distributions and restricted co-assembly in mammalian brain. The heterogeneous composition of Kv1 channels has made it difficult to use specific toxins to label brain structures. We used autoradiography to analyse the competitive behaviour of three Kv1 channel toxins--alpha-dendrotoxin, kaliotoxin, and mast cell degranulating peptide--for binding to kaliotoxin binding sites in various brain structures. IC(50) varied considerably between brain regions (by up to three orders of magnitude) for each ligand. alpha-dendrotoxin and kaliotoxin competed equally in some regions and to different extents in others, identifying two types of structure. Mast cell degranulating peptide competed with (125)I-kaliotoxin less efficiently than alpha-dendrotoxin and kaliotoxin, in all regions. Thus, differences in the capacity of these three toxins to bind to kaliotoxin binding sites provide evidence of major differences in the composition of the Kv1 channels constituting the kaliotoxin binding sites.
Bessone
Richard
R
ITIS, CNRS-UMR 6150, IFR Jean Roche, Faculté de Médecine de Marseille, Université de la Méditerranée, Boulevard Pierre Dramard 13916 Marseille, France.
Martin-Eauclaire
Marie-France
MF
Crest
Marcel
M
Mourre
Christiane
C
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000378:metabolism; D008297:Male; D015221:Potassium Channels / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000378:metabolism*
D004546:Elapid Venoms; D015221:Potassium Channels; D012604:Scorpion Venoms; C072276:kaliotoxin; C020273:dendrotoxin