Activity-dependent adenosine release may be linked to activation of Na(+)-K(+) ATPase: an in vitro rat study.
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 AT...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3906196?pdf=render |
| _version_ | 1818595819669946368 |
|---|---|
| author | Robert Edward Sims Nicholas Dale |
| author_facet | Robert Edward Sims Nicholas Dale |
| author_sort | Robert Edward Sims |
| collection | DOAJ |
| description | 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 Ca(2+), 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. |
| first_indexed | 2024-12-16T11:22:05Z |
| format | Article |
| id | doaj.art-a51318acc5c64e24b66977f4bff02bdd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T11:22:05Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a51318acc5c64e24b66977f4bff02bdd2022-12-21T22:33:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8748110.1371/journal.pone.0087481Activity-dependent adenosine release may be linked to activation of Na(+)-K(+) ATPase: an in vitro rat study.Robert Edward SimsNicholas DaleIn 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 Ca(2+), 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.http://europepmc.org/articles/PMC3906196?pdf=render |
| spellingShingle | Robert Edward Sims Nicholas Dale Activity-dependent adenosine release may be linked to activation of Na(+)-K(+) ATPase: an in vitro rat study. PLoS ONE |
| title | Activity-dependent adenosine release may be linked to activation of Na(+)-K(+) ATPase: an in vitro rat study. |
| title_full | Activity-dependent adenosine release may be linked to activation of Na(+)-K(+) ATPase: an in vitro rat study. |
| title_fullStr | Activity-dependent adenosine release may be linked to activation of Na(+)-K(+) ATPase: an in vitro rat study. |
| title_full_unstemmed | Activity-dependent adenosine release may be linked to activation of Na(+)-K(+) ATPase: an in vitro rat study. |
| title_short | Activity-dependent adenosine release may be linked to activation of Na(+)-K(+) ATPase: an in vitro rat study. |
| title_sort | activity dependent adenosine release may be linked to activation of na k atpase an in vitro rat study |
| url | http://europepmc.org/articles/PMC3906196?pdf=render |
| work_keys_str_mv | AT robertedwardsims activitydependentadenosinereleasemaybelinkedtoactivationofnakatpaseaninvitroratstudy AT nicholasdale activitydependentadenosinereleasemaybelinkedtoactivationofnakatpaseaninvitroratstudy |