Control of basal extracellular adenosine concentration in rat cerebellum
Wall, M. (Mark), Atterbury, Alison and Dale, Nicholas. (2007) Control of basal extracellular adenosine concentration in rat cerebellum. Journal of Physiology, Vol.582 (No.1). pp. 137-151. ISSN 0022-3751Full text not available from this repository.
Official URL: http://dx.doi.org/10.1113/jphysiol.2007.132050
To re-examine how the basal extracellular concentration of adenosine is regulated in acutely isolated cerebellar slices we have combined electrophysiological and microelectrode biosensor measurements. In almost all cases, synaptic transmission was tonically inhibited by adenosine acting via A(1) receptors. By contrast, in most slices, the biosensors did not measure an adenosine tone but did record a spatially non-uniform extracellular tone of the downstream metabolites (inosine and hypoxanthine). Most of the extracellular hypoxanthine arose from the metabolism of inosine by ecto-purine nucleoside phosphorylase (PNP). Adenosine kinase was the major determinant of adenosine levels, as its inhibition increased both adenosine concentration and A(1) receptor-mediated synaptic inhibition. Breakdown of adenosine by adenosine deaminase was the major source of the inosine/hypoxanthine tone. However adenosine deaminase played a minor role in determining the level of adenosine at synapses, suggesting a distal location. Blockade of adenosine transport (by NBTI/dipyridamole) had inconsistent effects on basal levels of adenosine and synaptic transmission. Unexpectedly, application of NBTI/dipyridamole prevented the efflux of adenosine resulting from block of adenosine kinase at only a subset of synapses. We conclude that there is spatial variation in the functional expression of NBTI/dipyridamole-sensitive transporters. The increased spatial and temporal resolution of the purine biosensor measurements has revealed the complexity of the control of adenosine and purine tone in the cerebellum.
|Item Type:||Journal Article|
|Subjects:||R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Q Science > QP Physiology
|Divisions:||Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)|
|Journal or Publication Title:||Journal of Physiology|
|Publisher:||Wiley-Blackwell Publishing Ltd.|
|Date:||1 July 2007|
|Number of Pages:||15|
|Page Range:||pp. 137-151|
|Access rights to Published version:||Restricted or Subscription Access|
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