Details

Autor(en) / Beteiligte

• Petravicz, Jeremy
• Fiacco, Todd A
• McCarthy, Ken D

Titel

Loss of IP sub(3) Receptor-Dependent Ca super(2+) Increases in Hippocampal Astrocytes Does Not Affect Baseline CA1 Pyramidal Neuron Synaptic Activity

Ist Teil von

• The Journal of neuroscience, 2008-05, Vol.28 (19), p.4967-4973

Erscheinungsjahr

2008

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Astrocytes in the hippocampus release calcium (Ca super(2+)) from intracellular stores intrinsically and in response to activation of G sub(q)-linked G-protein-coupled receptors (GPCRs) through the binding of inositol 1,4,5-trisphosphate (IP sub(3)) to its receptor (IP sub(3)R). Astrocyte Ca super(2+) has been deemed necessary and sufficient to trigger the release of gliotransmitters, such as ATP and glutamate, from astrocytes to modulate neuronal activity. Several lines of evidence suggest that IP sub(3)R type 2 (IP sub(3)R2) is the primary IP sub(3)R expressed by astrocytes. To determine whether IP sub(3)R2 is the primary functional IP sub(3)R responsible for astrocytic Ca super(2+) increases, we conducted experiments using an IP sub(3)R2 knock-out mouse model (IP sub(3)R2 KO). We show, for the first time, that lack of IP sub(3)R2 blocks both spontaneous and G sub(q)-linked GPCR-mediated increases in astrocyte Ca super(2+). Furthermore, neuronal G sub(q)-linked GPCR Ca super(2+) increases remain intact, suggesting that IP sub(3)R2 does not play a major functional role in neuronal calcium store release or may not be expressed in neurons. Additionally, we show that lack of IP sub(3)R2 in the hippocampus does not affect baseline excitatory neuronal synaptic activity as measured by spontaneous EPSC recordings from CA1 pyramidal neurons. Whole-cell recordings of the tonic NMDA receptor-mediated current indicates that ambient glutamate levels are also unaffected in the IP sub(3)R2 KO. These data show that IP sub(3)R2 is the key functional IP sub(3)R driving G sub(q)-linked GPCR-mediated Ca super(2+) increases in hippocampal astrocytes and that removal of astrocyte Ca super(2+) increases does not significantly affect excitatory neuronal synaptic activity or ambient glutamate levels.