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UNIVERSITY OF BUCHAREST
FACULTY OF PHYSICS Guest
2024-11-22 2:03 |
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Conference: Bucharest University Faculty of Physics 2004 Meeting
Section: Electricity and Biophysics
Title:
Decreased 5-HT1A-mediated GIRK Current in Dorsal Raphe Neurons of Knock-out 5-HTT-/- Mice
Authors:
Beatrice Macri**, Thierry Jacquin**, Patricia Bonnavion**,
Adela Marin*, Maria-Luiza Flonta*
Affiliation:
*Department of Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei, 91-95, R-050095, Bucharest, Romania
**INSERM U288, Laboratory of NeuroPsychoPharmacology, Faculty of Medecine Pitie-Salpetriere, 91, Bd de l`Hopital, 75634, Paris Cedex 13, France
Address for correspondence: macri_beatrice@hotmail.com
E-mail
macri_beatrice@hotmail.com
Keywords:
Serotonin, 5-HT1A, GIRK current, raphe, desensitization
Abstract:
Serotonin 5-HT1A receptors in the dorsal raphe nucleus (DRN) of mice devoid of the serotonin transporter (5-HTT-/-) exhibit a functional desensitization. Desensitization of 5-HT1A autoreceptors of dorsal raphe neurons in 5-HTT-/- mice has been attributed to a down regulation of 5-HT1A receptors and related G-proteins (Fabre et al., 2000). 5-HT1A autoreceptors can activate the G-protein inwardly rectifying K+ current (GIRK) (Penington et al., 1993). Activation of the GIRK current by 5-HT1A autoreceptors in DRN neurons of the rat induces membrane hyperpolarization and decreases spontaneous spike discharge (Penington et al., 1993). This is of functional importance because 5-HT1A receptor signaling is involved in major psychiatric diseases, in particular mood disorders such as depression. The goal of this study was to test the effect of 400 nM GppNHp (a non-hydrolysable analogue of GTP) on the spike discharge frequency and on the GIRK amplitude, for 5-HTT-/- and wild-type mice. Whole-cell patch-clamp recordings in the dorsal raphe nucleus (DRN) were obtained from 60 cells of wild-type mice and from 27 cells of 5-HTT-/- knock-out mice of the same C57Bl/6 genetic background. Cells were located throughout the rostro-caudal extent of the DRN (plates 65-72; Franklin & Paxinos, 1997), mostly in the dorsal subdivision of the nucleus (n = 33, 85% in wild type mice and n = 18, 75% in 5-HTT-/- knock-out mice). The electrophysiological properties measured in DRN neurons of 5-HTT+/+ and 5-HTT-/- knock-out mice were resting membrane potential, input resistance, membrane time constant of voltage response to a 20 pA hyperpolarizing current pulse, as well as amplitude and duration of action potential and afterhyperpolarization (AHP), and time constant of the initial phase of the AHP. Our study demonstrates that the decreased response to 5-HT1A receptor agonists in 5-HTT-/- mutants reflects alteration in 5-HT1A autoreceptor signaling upstream from the coupled GIRK current.
Keywords: Serotonin, 5-HT1A, GIRK current, raphe, desensitization
References
Fabre, V., Beaufour, C., Evrard, A., Rioux, A., Hanoun, N., Lesch, K.P., Murphy, D.L., Lanfumey, L., Hamon, M. & Martres, M.P. (2000) Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5-HT transporter. Eur. J. Neurosci., 12: 2299-2310.
Franklin, K.B.J. & Paxinos, G. (1997) The mouse brain in stereotaxic coordinates. Academic Press, Inc., San Diego, USA.
Penington, N.J., Kelly, J.S. & Fox, A.P. (1993) Whole-cell recording of inwardly rectifying K+ currents activated by 5-HT1A receptors on dorsal raphe neurons of the adult rat. J. Physiol. (Lond.), 469: 387-405.
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