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

2008; Society for Neuroscience; Volume: 28; Issue: 19 Linguagem: Inglês

10.1523/jneurosci.5572-07.2008

1529-2401

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

Ion channel regulation and function

Astrocytes in the hippocampus release calcium (Ca 2+ ) from intracellular stores intrinsically and in response to activation of G q -linked G-protein-coupled receptors (GPCRs) through the binding of inositol 1,4,5-trisphosphate (IP 3 ) to its receptor (IP 3 R). Astrocyte Ca 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 3 R type 2 (IP 3 R2) is the primary IP 3 R expressed by astrocytes. To determine whether IP 3 R2 is the primary functional IP 3 R responsible for astrocytic Ca 2+ increases, we conducted experiments using an IP 3 R2 knock-out mouse model (IP 3 R2 KO). We show, for the first time, that lack of IP 3 R2 blocks both spontaneous and G q -linked GPCR-mediated increases in astrocyte Ca 2+ . Furthermore, neuronal G q -linked GPCR Ca 2+ increases remain intact, suggesting that IP 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 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 3 R2 KO. These data show that IP 3 R2 is the key functional IP 3 R driving G q -linked GPCR-mediated Ca 2+ increases in hippocampal astrocytes and that removal of astrocyte Ca 2+ increases does not significantly affect excitatory neuronal synaptic activity or ambient glutamate levels.