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The dynamics of single spike-evoked adenosine release in the cerebellum

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Klyuch, Boris P., Richardson, Magnus J. E., Dale, Nicholas and Wall, M. (Mark). (2011) The dynamics of single spike-evoked adenosine release in the cerebellum. Journal of Physiology, The, Vol.589 (No.2). pp. 283-295. ISSN 0022-3751

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Official URL: http://dx.doi.org/10.1113/jphysiol.2010.198986

Abstract

The purine adenosine is a potent neuromodulator in the brain, with roles in a number
of diverse physiological and pathological processes. Modulators such as adenosine are difficult
to study as once released they have a diffuse action (which can affect many neurones) and,
unlike classical neurotransmitters, have no inotropic receptors. Thus rapid postsynaptic currents
(PSCs) mediated by adenosine (equivalent to mPSCs) are not available for study. As a result
the mechanisms and properties of adenosine release still remain relatively unclear. We have
studied adenosine release evoked by stimulating the parallel fibres in the cerebellum. Using
adenosine biosensors combined with deconvolution analysis and mathematical modelling, we
have characterised the release dynamics and diffusion of adenosine in unprecedented detail.
By partially blocking K+ channels, we were able to release adenosine in response to a single
stimulus rather than a train of stimuli. This allowed reliable sub-second release of reproducible
quantities of adenosine with stereotypic concentration waveforms that agreed well with predictions
of a mathematical model of purine diffusion. We found no evidence for ATP release
and thus suggest that adenosine is directly released in response to parallel fibre firing and does
not arise from extracellular ATP metabolism. Adenosine release events showed novel short-term
dynamics, including facilitated release with paired stimuli at millisecond stimulation intervals
but depletion-recovery dynamics with paired stimuli delivered over minute time scales. These
results demonstrate rich dynamics for adenosine release that are placed, for the first time, on a
quantitative footing and show strong similarity with vesicular exocytosis.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010) Faculty of Science > Life Sciences (2010- ) Faculty of Science > Centre for Systems Biology
Library of Congress Subject Headings (LCSH):	Adenosine -- Physiological transport, Cerebellum
Journal or Publication Title:	Journal of Physiology, The
Publisher:	Wiley-Blackwell Publishing Ltd.
ISSN:	0022-3751
Official Date:	15 January 2011
Volume:	Vol.589
Number:	No.2
Page Range:	pp. 283-295
Identification Number:	10.1113/jphysiol.2010.198986
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Medical Research Council (Great Britain) (MRC), Research Councils UK (RCUK)
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URI:	http://wrap.warwick.ac.uk/id/eprint/4463