Atterbury, Alison and Wall, Mark J.. (2011) A population of immature cerebellar parallel fibre synapses are insensitive to adenosine but are inhibited by hypoxia. Neuropharmacology, Vol.61 (No.4). pp. 880-888. ISSN 00283908

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Abstract

The purine adenosine plays an important role in a number of physiological and pathological processes and is neuroprotective during hypoxia and ischemia. The major effect of adenosine is to suppress network activity via the activation of A1 receptors. Here we report that in immature cerebellar slices, the activation of A1 receptors has variable effects on parallel fibre synaptic transmission, ranging from zero depression to an almost complete abolition of transmission. Concentration–response curves suggest that the heterogeneity of inhibition stems from differences in A1 receptor properties which could include coupling to downstream effectors. There is less variation in the effects of adenosine at parallel fibre synapses in slices from older rats and thus adenosine signalling appears developmentally regulated. In the cerebellum, hypoxia increases the concentration of extracellular adenosine leading to the activation of A1 receptors (at adenosine-sensitive parallel fibre synapses) and the suppression of glutamate release. It would be predicted that the synapses that were insensitive to adenosine would be less depressed by hypoxia and thus maintain function during metabolic stress. However those synapses which were insensitive to adenosine were rapidly inhibited by hypoxia via a mechanism which was not reversed by blocking A1 receptors. Thus another mechanism must be responsible for the hypoxia-mediated depression at these synapses. These different mechanisms of depression may be important for cell survival and for maintenance of cerebellar function following oxygen starvation.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Adenosine -- Physiological effect, Cerebellum, Cerebral anoxia
Journal or Publication Title:	Neuropharmacology
Publisher:	Pergamon
ISSN:	00283908
Date:	September 2011
Volume:	Vol.61
Number:	No.4
Page Range:	pp. 880-888
Identification Number:	10.1016/j.neuropharm.2011.06.006
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), University of Warwick
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URI:	http://wrap.warwick.ac.uk/id/eprint/36565

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