Title

Iptakalim Inhibits Nicotinic Acetylcholine Receptor-Mediated Currents In Dopamine Neurons Acutely Dissociated From Rat Substantia Nigra Pars Compacta

Department

neurobiology

Document Type

Article

Abstract

Iptakalim hydrochloride, a novel cardiovascular ATP-sensitive K+ (KATP) channel opener, has shown remarkable antihypertensive and neuroprotective effects in a variety of studies using in vivo and in vitro preparations. We recently found that iptakalim blocked human α4-containing nicotinic acetylcholine receptors (nAChRs) heterologously expressed in the human SH-EP1 cell line. In the present study, we examined the effects of iptakalim on several neurotransmitter-induced current responses in single DA neurons freshly dissociated from rat substantia nigra pars compacta (SNc), using perforated patch-clamp recordings combined with a U-tube rapid drug application. In identified DA neurons under voltage-clamp configuration, glutamate-, NMDA-, and GABA-induced currents were insensitive to co-application with iptakalim (100 μM), while whole-cell currents induced by ACh (1 mM + 1 μM atropine) or an α4β2 nicotinic acetylcholine receptors relatively selective agonist, RJR-2403 (300 μM), were eliminated by iptakalim. Iptakalim inhibited RJR-2403-induced current in a concentration-dependent manner, and reduced maximal RJR-2403-induced currents at the highest agonist concentration, suggesting a non-competitive block. In current-clamp mode, iptakalim failed to affect resting membrane potential and spontaneous action potential firing, but abolished RJR-2403-induced neuronal firing acceleration. Together, these results indicate that in dissociated SNc DA neurons, α4-containing nAChRs, rather than ionotropic glutamate receptors, GABAA receptors or perhaps K-ATP channels are the sensitive targets to mediate iptakalim's pharmacological roles. © 2006 Elsevier Ireland Ltd. All rights reserved.

Publication Date

7-31-2006

Publication Title

Neuroscience Letters

ISSN

03043940

Volume

403

Issue

2019-01-02 00:00:00

First Page

57

Last Page

62

Digital Object Identifier (DOI)

10.1016/j.neulet.2006.04.060

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