Gender‐dependent regulation of G‐protein‐gated inwardly rectifying potassium current in dorsal raphe neurons in knock‐out mice devoid of the 5‐hydroxytryptamine transporter |
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Authors: | Alexandre Julien Chu Loucif Patricia Bonnavion Batrice Macri Jean‐Louis Golmard Claudette Boni Maxette Melfort Grgoire Leonard Klaus‐Peter Lesch Joëlle Adrien Thierry Didier Jacquin |
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Institution: | Alexandre Julien Châu Loucif,Patricia Bonnavion,Béatrice Macri,Jean‐Louis Golmard,Claudette Boni,Maxette Melfort,Grégoire Leonard,Klaus‐Peter Lesch,Joëlle Adrien,Thierry Didier Jacquin |
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Abstract: | Agonists at G‐protein‐coupled receptors in neurons of the dorsal raphe nucleus (DRN) of knock‐out mice devoid of the serotonin transporter (5‐HTT?/?) exhibit lower efficacy to inhibit cellular discharge than in wild‐type counterparts. Using patch‐clamp whole‐cell recordings, we found that a G‐protein‐gated inwardly rectifying potassium (GIRK) current is involved in the inhibition of spike discharge induced by 5‐HT1A agonists (5‐carboxamidotryptamine (5‐CT) and (±)‐2‐dipropylamino‐8‐hydroxy‐1,2,3,4‐tetrahydronaphthalene hydrobromide (8‐OH‐DPAT); 50 nM–30 μM) in both wild‐type and 5‐HTT?/? female and male mice. These effects were mimicked by 5′‐guanylyl‐imido‐diphosphate (Gpp(NH)p; 400 μM) dialysis into cells with differences between genders. The 5‐HTT?/? knock‐out mutation reduced the current density induced by Gpp(NH)p in females but not in males. These data suggest that the decreased response of 5‐HT1A receptors to agonists in 5‐HTT?/? mutants reflects notably alteration in the coupling between G‐proteins and GIRK channels in females but not in males. Accordingly, gender differences in central 5‐HT neurotransmission appear to depend—at least in part—on sex‐related variations in corresponding receptor‐G protein signaling mechanisms. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 |
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Keywords: | 5‐HT1A 5‐CT 8‐OH‐DPAT Gpp(NH)p functional desensitization |
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