title: Margatoxin increases dopamine release in rat striatum via voltage-gated K+ channels.
abstract: 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.
authors.affiliation: Department of Psychiatry, University Hospital, Innsbruck, Austria. alois.saria@uibk.ac.at
authors.forename: A
authors.initials: A
authors.lastname: Saria
authors.forename: C V
authors.initials: CV
authors.lastname: Seidl
authors.forename: H S
authors.initials: HS
authors.lastname: Fischer
authors.forename: R O
authors.initials: RO
authors.lastname: Koch
authors.forename: S
authors.initials: S
authors.lastname: Telser
authors.forename: S G
authors.initials: SG
authors.lastname: Wanner
authors.forename: C
authors.initials: C
authors.lastname: Humpel
authors.forename: M L
authors.initials: ML
authors.lastname: Garcia
authors.forename: H G
authors.initials: HG
authors.lastname: Knaus
mesh_terms: 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
chemical_list: D007457:Iodine Radioisotopes; D009498:Neurotoxins; D010455:Peptides; D015221:Potassium Channels; D012604:Scorpion Venoms; D014316:Tritium; D018999:Charybdotoxin; C077910:margatoxin; C064719:iberiotoxin; D004298:Dopamine