Margatoxin increases dopamine release in rat striatum via voltage-gated K+ channels.
The distribution of iodinated margatoxin ([125I]margatoxin) binding sites in rat was investigated by autoradiography. Rat striatum expresses a high density of margatoxin binding sites and, therefore, the effects of margatoxin, charybdotoxin and iberiotoxin have been studied on [3H]dopamine release from rat striatal slices in vitro. Margatoxin (0.1-100 nM) and charybdotoxin (10-1000 nM), but not iberiotoxin increased the spontaneous and the electrically evoked [3H]dopamine release. [3H]dopamine release by margatoxin was inhibited by tetrodotoxin and omega-conotoxin GVIA, but not by atropine, naloxone, N(omega)-nitro-L-arginine and neurokinin or neurotensin receptor antagonists. In the buffer solution used for release experiments, [125I]margatoxin labels a maximum of 0.12 pmol of sites/mg protein in rat striatal membranes with a Kd of 5 pM. [125I]margatoxin binding was inhibited by margatoxin (Ki of 4 pM), charybdotoxin (Ki of 162 pM) but not by iberiotoxin. We conclude that inhibition of margatoxin-sensitive voltage-gated K+ channels increases [3H]dopamine release demonstrating their role in repolarization of nigrostriatal projections. In contrast, iberiotoxin-sensitive, high-conductance Ca2+-activated K+ channels are not involved in release of [3H]dopamine.
Saria
A
A
Department of Psychiatry, University Hospital, Innsbruck, Austria. alois.saria@uibk.ac.at
Seidl
C V
CV
Fischer
H S
HS
Koch
R O
RO
Telser
S
S
Wanner
S G
SG
Humpel
C
C
Garcia
M L
ML
Knaus
H G
HG
D000818:Animals; D001665:Binding Sites; D018999:Charybdotoxin / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D007457:Iodine Radioisotopes; D015640:Ion Channel Gating; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms; D014316:Tritium
D007457:Iodine Radioisotopes; D009498:Neurotoxins; D010455:Peptides; D015221:Potassium Channels; D012604:Scorpion Venoms; D014316:Tritium; D018999:Charybdotoxin; C077910:margatoxin; C064719:iberiotoxin; D004298:Dopamine