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Intracellular acidification causes adenosine release during states of hyperexcitability in the hippocampus

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Dulla, Chris G., Frenguelli, Bruno G., Staley, Kevin and Masino, Susan A.. (2009) Intracellular acidification causes adenosine release during states of hyperexcitability in the hippocampus. Journal of Neurophysiology, Vol.102 (No.3). pp. 1984-1993. ISSN 0022-3077

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Official URL: http://dx.doi.org/10.1152/jn.90695.2008

Abstract

Dulla CG, Frenguelli BG, Staley KJ, Masino SA. Intracellular acidification causes adenosine release during states of hyperexcitability in the hippocampus. J Neurophysiol 102: 1984-1993, 2009. First published July 22, 2009; doi:10.1152/jn.90695.2008. Decreased pH increases extracellular adenosine in CNS regions as diverse as hippocampus and ventral medulla. However, thus far there is no clear consensus whether the critical pH change is a decrease in intracellular and/or extracellular pH. Previously we showed that a decrease in extracellular pH is necessary and a decrease in intracellular pH alone is not sufficient, to increase extracellular adenosine in an acute hippocampal slice preparation. Here we explored further the role of intracellular pH under different synaptic conditions in the hippocampal slice. When synaptic excitability was increased, either during gamma-aminobutyric acid type A receptor blockade in CA1 or after the induction of persistent bursting in CA3, a decrease in intracellular pH alone was now sufficient to: 1) elevate extracellular adenosine concentration, 2) activate adenosine A 1 receptors, 3) decrease excitatory synaptic transmission (CA1), and 4) attenuate burst frequency in an in vitro seizure model (CA3). Hippocampal slices obtained from adenosine A 1 receptor knockout mice did not exhibit these pH-mediated effects on synaptic transmission, further confirming the role of adenosine acting at the adenosine A 1 receptor. Taken together, these data strengthen and add significantly to the evidence outlining a change in pH as an important stimulus influencing extracellular adenosine. In addition, we identify conditions under which intracellular pH plays a dominant role in regulating extracellular adenosine concentrations.

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)

Library of Congress Subject Headings (LCSH):

Adenosine, Hippocampus (Brain), Molecular neurobiology, Excitation (Physiology), Neural transmission

Journal or Publication Title:

Journal of Neurophysiology

Publisher:

American Physiological Society

ISSN:

0022-3077

Official Date:

September 2009

Dates:

Date	Event
September 2009	Published

Volume:

Vol.102

Number:

No.3

Number of Pages:

Page Range:

pp. 1984-1993

Identification Number:

10.1152/jn.90695.2008

Status:

Peer Reviewed

Publication Status:

Published

Access rights to Published version:

Restricted or Subscription Access

Funder:

American Epilepsy Foundation, Epilepsy Research UK, National Institute of Neurological Disorders and Stroke (U.S.), National Science Foundation (U.S.) (NSF), Howard Hughes Medical Institute

Grant number:

NS-34360-12 (NINDS), NS-29173 (NSF), NS-61290 (NSF)

Version or Related Resource:

Dulla, C.G., et al. (2008). Intracellular acidification causes adenosine release during states of hyperexcitability in the hippocampus. [Abstract]. Purinergic Signalling, 4(1), pp. S160-S161. http://wrap.warwick.ac.uk/id/eprint/29355

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