Neuronal adenosine release, and not astrocytic ATP release, mediates feedback inhibition of excitatory activity
- 15 March 2012
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 109 (16), 6265-6270
- https://doi.org/10.1073/pnas.1120997109
Abstract
Adenosine is a potent anticonvulsant acting on excitatory synapses through A1 receptors. Cellular release of ATP, and its subsequent extracellular enzymatic degradation to adenosine, could provide a powerful mechanism for astrocytes to control the activity of neural networks during high-intensity activity. Despite adenosine's importance, the cellular source of adenosine remains unclear. We report here that multiple enzymes degrade extracellular ATP in brain tissue, whereas only Nt5e degrades AMP to adenosine. However, endogenous A1 receptor activation during cortical seizures in vivo or heterosynaptic depression in situ is independent of Nt5e activity, and activation of astrocytic ATP release via Ca2+ photolysis does not trigger synaptic depression. In contrast, selective activation of postsynaptic CA1 neurons leads to release of adenosine and synaptic depression. This study shows that adenosine-mediated synaptic depression is not a consequence of astrocytic ATP release, but is instead an autonomic feedback mechanism that suppresses excitatory transmission during prolonged activity.This publication has 50 references indexed in Scilit:
- Local disruption of glial adenosine homeostasis in mice associates with focal electrographic seizures: A first step in epileptogenesis?Glia, 2011
- Astrocytes Control Breathing Through pH-Dependent Release of ATPScience, 2010
- Prostatic Acid Phosphatase Is Expressed in Peptidergic and Nonpeptidergic Nociceptive Neurons of Mice and RatsPLOS ONE, 2010
- Distribution of ectonucleotidases in the rodent brain revisitedCell and tissue research, 2008
- Connexin 43 Hemichannels Are Permeable to ATPJournal of Neuroscience, 2008
- Adenosine as a neuromodulator in neurological diseasesCurrent Opinion in Pharmacology, 2008
- A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and FunctionJournal of Neuroscience, 2008
- Specificity of the ecto‐ATPase inhibitor ARL 67156 on human and mouse ectonucleotidasesBritish Journal of Pharmacology, 2007
- Adenosine dysfunction in astrogliosis: cause for seizure generation?Neuron Glia Biology, 2007
- Development of an HPLC method for determination of metabolic compounds in myocardial tissueJournal of Pharmaceutical and Biomedical Analysis, 2004