Dokument: GABA-Induced Ca2+-Signaling in Rat Hippocampal Astrocytes

Titel:	GABA-Induced Ca2+-Signaling in Rat Hippocampal Astrocytes
URL für Lesezeichen:	https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=6840
URN (NBN):	urn:nbn:de:hbz:061-20080128-105117-3
Kollektion:	Dissertationen
Sprache:	Englisch
Dokumententyp:	Wissenschaftliche Abschlussarbeiten » Dissertation
Medientyp:	Text
Autor:	Meier, Silke D. [Autor]
Dateien:	[Dateien anzeigen] Adobe PDF [Details] 13,48 MB in einer Datei [ZIP-Datei erzeugen] Dateien vom 27.01.2008 / geändert 27.01.2008
Beitragende:	Prof. Dr. Rose, Christine R. [Gutachter] Prof. Dr. Müller, Hans Werner [Gutachter] Prof. Dr. Reichenbach, Andreas [Gutachter]
Stichwörter:	development, fura-2, GABA(A), GABA(B), sulforhodamine101
Dewey Dezimal-Klassifikation:	500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie
Beschreibung:	GABA (gamma-aminobutyric acid), the predominant inhibitory neurotransmitter in the mature mammalian brain, is excitatory for neurons during early development upon GABA(A) receptor activation. In astrocytes, GABA induces intracellular Ca2+ transients by activation of both, GABA(A) and GABA(B) receptors. GABA(B) receptor-mediated [Ca2+]i increases are involved in neuron-glia interaction by potentiating inhibitory synaptic transmission (Kang et al., 1998) and by causing heterosynaptic depression (Serrano et al., 2006). Given that GABA(B) receptors couple to Gi/o proteins in neurons and inhibit presynaptic Ca2+ channels, the observed [Ca2+]i increase in astrocytes is an unexpected finding. Hence, the aims of the present study were (1) to elucidate the mechanism of GABA-induced Ca2+ transients in astrocytes and (2) to establish a developmental profile of astrocytic Ca2+ responses. To this end, I performed Ca2+ imaging with Fura-2 in combination with whole-cell patch-clamp recordings in acute rat hippocampal slices. For the identification of astrocytes, I adapted a method which had originally been introduced for the identification of cortical astrocytes in vivo (Nimmerjahn et al., 2004). Astrocytes were stained with the red fluorescent dye sulforhodamine 101 (SR101). The specificity of SR101 for astrocytes in acute hippocampal slices at young postnatal stages (P03 and P15) was confirmed with electrophysiological recordings. Local pressure application of GABA (100 ms, 1 mM) to SR101-positive cells induced intracellular Ca2+ transients, which were mediated by both GABA(A) and GABA(B) receptors. Muscimol, a specific GABA(A) receptor agonist, depolarized astrocytes and resulted in Ca2+ influx through voltage-gated Ca2+ channels, confirming earlier studies. This mechanism was the same throughout the developmental period investigated (P03 and P15). GABA(B) receptor activation, in contrast, resulted in delayed Ca2+ transients that were due to G-protein activation and Ca2+ release from IP3-sensitive intracellular Ca2+ stores. An interaction of GABA(B) receptors with metabotropic glutamate receptors, as has been described in the cerebellum (Hirono et al., 2001; Tabata et al., 2004), might also be the case in hippocampal astrocytes. While GABA(A) receptor-activation induced Ca2+ transients in 70-100% of astrocytes throughout development (P03 to P33±1), GABA(B) receptor-mediated Ca2+ signaling exhibited a clear developmental profile. The amount of astrocytes responding with a [Ca2+]i increase upon GABA(B) receptor-activation showed a bell-shaped distribution with a maximum of 60% of cells responding during the second postnatal week (P11 to P15). This developmental profile of GABA(B) receptor-mediated Ca2+ transients suggests that astrocytes play a role during postnatal maturation of the hippocampal network.
Lizenz:	Urheberrechtsschutz
Fachbereich / Einrichtung:	Mathematisch- Naturwissenschaftliche Fakultät » WE Biologie » Neurobiologie
Dokument erstellt am:	27.01.2008
Dateien geändert am:	27.01.2008
Promotionsantrag am:	26.09.2007
Datum der Promotion:	16.01.2008