Lopatář, Ján, Dale, Nicholas and Frenguelli, Bruno G. (2015) Pannexin-1-mediated ATP release from area CA3 drives mGlu5-dependent neuronal oscillations. Neuropharmacology, Volume 93 . pp. 219-228. doi:10.1016/j.neuropharm.2015.01.014 ISSN 0028-3908.

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Abstract

The activation of Group I metabotropic glutamate receptors (GI mGluRs) in the hippocampus results in the appearance of persistent bursts of synchronised neuronal activity. In response to other stimuli, such activity is known to cause the release of the purines ATP and its neuroactive metabolite, adenosine. We have thus investigated the potential release and role of the purines during GI mGluR-induced oscillations in rat hippocampal areas CA3 and CA1 using pharmacological techniques and microelectrode biosensors for ATP and adenosine. The GI mGluR agonist DHPG induced both persistent oscillations in neuronal activity and the release of adenosine in areas CA1 and CA3. In contrast, the DHPG-induced release of ATP was only observed in area CA3. Whilst adenosine acting at adenosine A1 receptors suppressed DHPG-induced burst activity, the activation of mGlu5 and P2Y1 ATP receptors were necessary for the induction of DHPG-induced oscillations. Selective inhibition of pannexin-1 hemichannels with a low concentration of carbenoxolone (10 μM) or probenecid (1 mM) did not affect adenosine release in area CA3, but prevented both ATP release in area CA3 and DHPG-induced bursting. These data reveal key aspects of GI mGluR-dependent neuronal activity that are subject to bidirectional regulation by ATP and adenosine in the initiation and pacing of burst firing, respectively, and which have implications for the role of GI mGluRs in seizure activity and neurodevelopmental disorders.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Adenosine, Connexins, Epilepsy -- Genetic aspects
Journal or Publication Title:	Neuropharmacology
Publisher:	Elsevier
ISSN:	0028-3908
Official Date:	June 2015
Dates:	Date Event June 2015 Published 31 January 2015 Available 15 August 2015 Accepted 29 August 2014 Submitted
Volume:	Volume 93
Number of Pages:	10
Page Range:	pp. 219-228
DOI:	10.1016/j.neuropharm.2015.01.014
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	30 December 2015
Date of first compliant Open Access:	27 June 2016
Funder:	Epilepsy Research UK

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