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Astrocytic adenosine kinase regulates basal synaptic adenosine levels and seizure activity but not activity-dependent adenosine release in the hippocampus.
- Source :
-
Neuropharmacology [Neuropharmacology] 2009 Feb; Vol. 56 (2), pp. 429-37. Date of Electronic Publication: 2008 Oct 10. - Publication Year :
- 2009
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Abstract
- Adenosine is an endogenous inhibitor of excitatory synaptic transmission with potent anticonvulsant properties in the mammalian brain. Given adenosine's important role in modulating synaptic transmission, several mechanisms exist to regulate its extracellular availability. One of these is the intracellular enzyme adenosine kinase (ADK), which phosphorylates adenosine to AMP. We have investigated the role that ADK plays in regulating the presence and effects of extracellular adenosine in area CA1 of rat hippocampal slices. Inhibition of ADK activity with 5'-iodotubercidin (IODO; 5 muM) raised extracellular adenosine, as measured with adenosine biosensors, and potently inhibited field excitatory post-synaptic potentials (fEPSPs) in an adenosine A(1)R-dependent manner. In nominally Mg(2+)-free aCSF, which facilitated the induction of electrically-evoked epileptiform activity, adenosine biosensor recordings revealed that seizures were accompanied by the transient release of adenosine. Under these conditions, IODO also inhibited the fEPSP and greatly suppressed epileptiform activity evoked by brief, high-frequency stimulation. During spontaneous seizures evoked by the A(1)R antagonist CPT, adenosine release was unaffected by IODO. This suggests that ADK activity does not limit activity-dependent adenosine release. On the basis of strong ADK immunoreactivity in GFAP-positive cells, astrocytes are likely to play a key role in regulating basal adenosine levels. It is this action of ADK on the basal adenosine tone that is permissive to seizure activity, and, by extension, other forms of activity-dependent neuronal activity such as synaptic plasticity.
- Subjects :
- Animals
Animals, Newborn
Astrocytes drug effects
Electric Stimulation methods
Enzyme Inhibitors pharmacology
Excitatory Postsynaptic Potentials drug effects
Excitatory Postsynaptic Potentials physiology
Glial Fibrillary Acidic Protein metabolism
Hippocampus drug effects
Hippocampus metabolism
In Vitro Techniques
Rats
Rats, Sprague-Dawley
Seizures etiology
Synapses drug effects
Theophylline analogs & derivatives
Theophylline pharmacology
Time Factors
Tubercidin analogs & derivatives
Tubercidin pharmacology
Adenosine metabolism
Adenosine Kinase metabolism
Astrocytes metabolism
Hippocampus cytology
Seizures metabolism
Synapses physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0028-3908
- Volume :
- 56
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 18957298
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2008.09.016