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Margatoxin Increases Dopamine Release in Rat Striatum via Voltage-Gated K+ Channels

Margatoxin Increases Dopamine Release in Rat Striatum via Voltage-Gated K+ Channels

A Saria, C V Seidl, H S Fischer, R O Koch, S Telser, S G Wanner, C Humpel, M L Garcia, H G Knaus

Eur J Pharmacol. 1998 Feb 19;343(2-3):193-200.

PMID: 9570467

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP145808475	Margatoxin		145808-47-5	Price

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