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Astrocytic adenosine kinase regulates basal synaptic adenosine levels and seizure activity but not activity-dependent adenosine release in the hippocampus

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Astrocytic adenosine kinase regulates basal synaptic adenosine levels and seizure activity but not activity-dependent adenosine release in the hippocampus. / Etherington, Lori-An V.; Patterson, Graham E.; Meechan, Louise; Boison, Detlev; Irving, Andrew J.; Dale, Nicholas; Frenguelli, Bruno G.

In: Neuropharmacology, Vol. 56, No. 2, 02.2009, p. 429-437.

Research output: Contribution to journalArticle

Harvard

Etherington, L-AV, Patterson, GE, Meechan, L, Boison, D, Irving, AJ, Dale, N & Frenguelli, BG 2009, 'Astrocytic adenosine kinase regulates basal synaptic adenosine levels and seizure activity but not activity-dependent adenosine release in the hippocampus' Neuropharmacology, vol 56, no. 2, pp. 429-437.

APA

Etherington, L-A. V., Patterson, G. E., Meechan, L., Boison, D., Irving, A. J., Dale, N., & Frenguelli, B. G. (2009). Astrocytic adenosine kinase regulates basal synaptic adenosine levels and seizure activity but not activity-dependent adenosine release in the hippocampus. Neuropharmacology, 56(2), 429-437doi: 10.1016/j.neuropharm.2008.09.016

Vancouver

Etherington L-AV, Patterson GE, Meechan L, Boison D, Irving AJ, Dale N et al. Astrocytic adenosine kinase regulates basal synaptic adenosine levels and seizure activity but not activity-dependent adenosine release in the hippocampus. Neuropharmacology. 2009 Feb;56(2):429-437.

Author

Etherington, Lori-An V.; Patterson, Graham E.; Meechan, Louise; Boison, Detlev; Irving, Andrew J.; Dale, Nicholas; Frenguelli, Bruno G. / Astrocytic adenosine kinase regulates basal synaptic adenosine levels and seizure activity but not activity-dependent adenosine release in the hippocampus.

In: Neuropharmacology, Vol. 56, No. 2, 02.2009, p. 429-437.

Research output: Contribution to journalArticle

Bibtex - Download

@article{cd127c0f64874917963e0875057e83e1,
title = "Astrocytic adenosine kinase regulates basal synaptic adenosine levels and seizure activity but not activity-dependent adenosine release in the hippocampus",
author = "Etherington, {Lori-An V.} and Patterson, {Graham E.} and Louise Meechan and Detlev Boison and Irving, {Andrew J.} and Nicholas Dale and Frenguelli, {Bruno G.}",
year = "2009",
volume = "56",
number = "2",
pages = "429--437",
journal = "Neuropharmacology",
issn = "0028-3908",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Astrocytic adenosine kinase regulates basal synaptic adenosine levels and seizure activity but not activity-dependent adenosine release in the hippocampus

A1 - Etherington,Lori-An V.

A1 - Patterson,Graham E.

A1 - Meechan,Louise

A1 - Boison,Detlev

A1 - Irving,Andrew J.

A1 - Dale,Nicholas

A1 - Frenguelli,Bruno G.

AU - Etherington,Lori-An V.

AU - Patterson,Graham E.

AU - Meechan,Louise

AU - Boison,Detlev

AU - Irving,Andrew J.

AU - Dale,Nicholas

AU - Frenguelli,Bruno G.

PY - 2009/2

Y1 - 2009/2

N2 - <p>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 mu M) raised extracellular adenosine, as measured with adenosine biosensors, and potently inhibited field excitatory post-synaptic 2 potentials (fEPSPs) in an adenosine A(1)R-dependent manner. In nominally Mg2+-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 AIR 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. (c) 2008 Elsevier Ltd. All rights reserved.</p>

AB - <p>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 mu M) raised extracellular adenosine, as measured with adenosine biosensors, and potently inhibited field excitatory post-synaptic 2 potentials (fEPSPs) in an adenosine A(1)R-dependent manner. In nominally Mg2+-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 AIR 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. (c) 2008 Elsevier Ltd. All rights reserved.</p>

KW - Adenosine kinase

KW - Seizure

KW - Adenosine

KW - Epilepsy

KW - Iodotubercidin

KW - Astrocytes

KW - RAT HIPPOCAMPUS

KW - EXTRACELLULAR ADENOSINE

KW - ENDOGENOUS ADENOSINE

KW - CA1 REGION

KW - INHIBITION

KW - SLICES

KW - HYPOXIA

KW - BRAIN

KW - EPILEPTOGENESIS

KW - RECEPTORS

U2 - 10.1016/j.neuropharm.2008.09.016

DO - 10.1016/j.neuropharm.2008.09.016

M1 - Article

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 2

VL - 56

SP - 429

EP - 437

ER -

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