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Activity-dependent adenosine release may be linked to activation of Na+-K+ ATPase : an in vitro rat study
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Sims, Robert E. and Dale, Nicholas (2014) Activity-dependent adenosine release may be linked to activation of Na+-K+ ATPase : an in vitro rat study. PLoS One, Volume 9 (Number 1). Article number e87481. doi:10.1371/journal.pone.0087481
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WRAP_Sims_journal.pone.0087481.pdf - Published Version Available under License Creative Commons Attribution. Download (2321Kb) | Preview |
Official URL: http://dx.doi.org/10.1371/journal.pone.0087481
Abstract
In the brain, extracellular adenosine increases as a result of neuronal activity. The mechanisms by which this occurs are only incompletely understood. Here we investigate the hypothesis that the Na+ influxes associated with neuronal signalling activate the Na+-K+ ATPase which, by consuming ATP, generates intracellular adenosine that is then released via transporters. By measuring adenosine release directly with microelectrode biosensors, we have demonstrated that AMPA-receptor evoked adenosine release in basal forebrain and cortex depends on extracellular Na+. We have simultaneously imaged intracellular Na+ and measured adenosine release. The accumulation of intracellular Na+ during AMPA receptor activation preceded adenosine release by some 90 s. By removing extracellular Ca2+, and thus preventing indiscriminate neuronal activation, we used ouabain to test the role of the Na+-K+ ATPase in the release of adenosine. Under conditions which caused a Na+ influx, brief applications of ouabain increased the accumulation of intracellular Na+ but conversely rapidly reduced extracellular adenosine levels. In addition, ouabain greatly reduced the amount of adenosine released during application of AMPA. Our data therefore suggest that activity of the Na+-K+ ATPase is directly linked to the efflux of adenosine and could provide a universal mechanism that couples adenosine release to neuronal activity. The Na+-K+ ATPase-dependent adenosine efflux is likely to provide adenosine-mediated activity-dependent negative feedback that will be important in many diverse functional contexts including the regulation of sleep.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QH Natural history > QH301 Biology | ||||
| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||
| Library of Congress Subject Headings (LCSH): | Adenosine , Neurons | ||||
| Journal or Publication Title: | PLoS One | ||||
| Publisher: | Public Library of Science | ||||
| ISSN: | 1932-6203 | ||||
| Official Date: | 29 January 2014 | ||||
| Dates: |
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| Date of first compliant deposit: | 26 December 2015 | ||||
| Volume: | Volume 9 | ||||
| Number: | Number 1 | ||||
| Page Range: | Article number e87481 | ||||
| DOI: | 10.1371/journal.pone.0087481 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Open Access | ||||
| Funder: | Wellcome Trust (London, England) | ||||
| Grant number: | WT087968MA (WT) |
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