Wall, Mark J. and Dale, Nicholas (2013) Neuronal transporter and astrocytic ATP exocytosis underlie activity-dependent adenosine release in the hippocampus. The Journal of Physiology, Volume 591 (Number 16). pp. 3853-3871. doi:10.1113/jphysiol.2013.253450 ISSN 0022-3751.

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Abstract

The neuromodulator adenosine plays an important role in many physiological and pathological processes within the mammalian CNS. However, the precise mechanisms of how the concentration of extracellular adenosine increases following neural activity remain contentious. Here we have used microelectrode biosensors to directly measure adenosine release induced by focal stimulation in stratum radiatum of area CA1 in mouse hippocampal slices. Adenosine release was both action potential and Ca2+ dependent and could be evoked with low stimulation frequencies and small numbers of stimuli. Adenosine release required the activation of ionotropic glutamate receptors and could be evoked by local application of glutamate receptor agonists. Approximately 40% of stimulated-adenosine release occurred by translocation of adenosine via equilibrative nucleoside transporters (ENTs). This component of release persisted in the presence of the gliotoxin fluoroacetate and thus results from the direct release of adenosine from neurons. A reduction of adenosine release in the presence of NTPDase blockers, in slices from CD73-/- and dn-SNARE mice, provides evidence that a component of adenosine release arises from the extracellular metabolism of ATP released from astrocytes. This component of release appeared to have slower kinetics than the direct ENT-mediated release of adenosine. These data suggest that activity-dependent adenosine release is surprisingly complex and, in the hippocampus, arises from at least two distinct mechanisms with different cellular sources.

Item Type:	Journal Article
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Journal or Publication Title:	The Journal of Physiology
Publisher:	Blackwell
ISSN:	0022-3751
Official Date:	August 2013
Dates:	Date Event August 2013 Published
Volume:	Volume 591
Number:	Number 16
Page Range:	pp. 3853-3871
DOI:	10.1113/jphysiol.2013.253450
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access

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