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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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
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)
References:	Beierlein M & RegehrWG (2006). Brief bursts of parallel fiber activity trigger calcium signals in Bergmann glia. J Neurosci 26, 6958–6967. Bellamy TC & Ogden D (2006). Long-term depression of neuron to glial signalling in rat cerebellar cortex. Eur J Neurosci 23, 581–586. Bordey A & Sontheimer H (2003). Modulation of glutamatergic transmission by Bergmann glial cells in rat cerebellum in situ. J Neurophysiol 89, 979–988. Boison D (2006). Adenosine kinase, epilepsy and stroke, mechanisms and therapies. Trends Pharmacol Sci 27, 652–658. Brasnjo G & Otis TS (2001) Neuronal glutamate transporters control activation of postsynaptic metabotropic glutamate receptors and influence cerebellar long-term depression. Neuron 31, 607–616. Clark BA & Barbour B (1997). Currents evoked in Bergmann glial cells by parallel fibre stimulation in rat cerebellar slices. J Physiol 502, 335–350. Craig CG &White TD (1993). N-Methyl-D-aspartate and non-N-methyl-D-aspartate-evoked adenosine release from rat cortical slices, distinct purinergic sources and mechanisms of release. J Neurochem60, 1073–1080. Dale N (1998). Delayed production of adenosine underlies temporal modulation of swimming in frog embryo. J Physiol 511, 265–272. Dale N, Gourine AV, Llaudet E, Bulmer D, Thomas T & Spyer KM (2002). Rapid adenosine release in the nucleus tractus solitarii during defence response in rats, real-time measurement in vivo. J Physiol 544, 149–160. Dale N & Frenguelli B (2009). Release of adenosine and ATP during ischemia and epilepsy. Curr Neuropharmacol 7, 160–179. Daniel H & Crepel F (2001). Control of Ca2+ influx by cannabinoid and metabotropic glutamate receptors in rat cerebellar cortex requires K+ channels. J Physiol 537, 793–800. Delaney AJ & Jahr CE (2002). Kainate receptors differentially regulate release at two parallel fiber synapses. Neuron 36, 475–482. Edwards FA, Gibb AJ & Colquhoun D (1992). ATP receptor-mediated synaptic currents in the central nervous system. Nature 359, 144–147. Fredholm BB, Arslan G, Halldner L, Kull B, Shulte G & WasswemanW(2000). Structure and function of adenosine receptors and their genes. Naunyn Schmiedebergs Arch Pharmacol 362, 364–374. Fredholm BB, Ijzerman AP, Jacobson KA, Klotz KN & Linden J (2001). International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53, 527–552. Isope P, Franconville R, Barbour B & Ascher P (2004). Repetitive firing of rat cerebellar parallel fibres after a single stimulation. J Physiol 554, 829–839. Jo YH & Schlichter R (1999). Synaptic co-release of ATP and GABA in cultured spinal neurons. Nat Neurosci 2, 241–245. Kimura M, Saitoh N & Takahashi T (2003). Adenosine A1 receptor-mediated presynaptic inhibition at the calyx of Held of immature rats. J Physiol 553, 415–426. Li J & Iadecola C (1994). Nitric oxide and adenosine mediate vasodilation during functional activation in cerebellar cortex. Neuropharmacol 33, 1453–1461. Llaudet E, Botting N, Crayston J & Dale N (2003). A three enzyme microelectrode sensor for detecting purine release from central nervous system. Biosens Bioelectron 18, 43–52. Llaudet E, Hatz S, DroniouM& Dale N (2005).Microelectrode biosensor for real-time measurement of ATP in biological tissue. Anal Chem 77, 3267–3273. Mart´ın ED, Fern´andez M, PereaG, Pascual O, Haydon PG, Araque A & Ce˜na V (2007). Adenosine released by astrocytes contributes to hypoxia-induced modulation of synaptic transmission. Glia 55, 36–45. Mitchell JB, Lupica CR & Dunwiddie TV (1993). Activity-dependent release of endogenous adenosine modulates synaptic responses in the rat hippocampus. J Neurosci 13, 3439–3447. Mitterdorfer J & Bean BP (2002). Potassium currents during the action potential of hippocampal CA3 neurons. J Neurosci 22, 10106–10115. Nedergaard S ( 1999). Regulation of action potential size and excitability in substantia nigra compacta neurons, sensitivity to 4-aminopyridine. J Neurophysiol 82, 2903–2913. Neher E & Sakaba T (2001). Combining deconvolution and noise analysis for the estimation of transmitter release rates at the calyx of Held. J Neurosci 21, 444–461. Pearson RA, Dale N, Llaudet E &Mobbs P (2005). ATP released via gap junction hemichannels from the pigment epithelium regulates neural retinal progenitor proliferation. Neuron 46, 731–744. Pearson T, Nuritova F, Caldwell D, Dale N & Frenguelli BG (2001). A depletable pool of adenosine in area CA1 of the rat hippocampus. J Neurosci 21, 2298–2307. Piet R & Jahr CE (2007). Glutamatergic and purinergic receptor-mediated calcium transients in Bergmann glial cells. J Neurosci 27, 4027–4035. Richardson MJE & Silberberg G (2008). Measurement and analysis of postsynaptic potentials using a novel voltage-deconvolution method. J Neurophysiol 99, 1020–1031. Rossi B,Maton G & Collin T (2008). Calcium-permeable presynaptic AMPA receptors in cerebellar molecular layer interneurones. J Physiol 586, 5129–5145. Sabatini BL & RegehrWG (1997). Control of neurotransmitter release by presynaptic waveform at the granule cell to Purkinje cell synapse. J Neurosci 17, 3425–3435. SweeneyMI ( 1996). Adenosine release and uptake in cerebellar granule neurons both occur via an equilibrative nucleoside carrier that is modulated by G proteins. J Neurochem67, 81–88. Tsodyks M & Markram H (1997). The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability. Proc Natl Acad Sci U S A 94, 719–723. Wall MJ & Dale N (2007). Auto-inhibition of parallel fibre–Purkinje cell synapses by activity dependent adenosine release. J Physiol 581, 553–566. Wall MJ & Dale N (2008). Activity-dependent release of adenosine: a critical re-evaluation of mechanism. Curr Neuropharmacol 6, 329–337. Wall MJ,Wigmore G, Lopat´ar J, Frenguelli BG & Dale N (2008). The novel NTPDase inhibitor sodium polyoxotungstate (POM-1) inhibits ATP breakdown but also blocks central synaptic transmission, an action independent of NTPDase inhibition. Neuropharmacol 55, 1251–1258. Wong YC, Billups B, Johnston J, Evans RJ & Forsythe ID (2006). Endogenous activation of adenosine A1 receptors but not P2X receptors during high-frequency synaptic transmission at the calyx of Held. J Neurophysiol 95, 3336–3342.
URI:	http://wrap.warwick.ac.uk/id/eprint/4463

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