Modulation of synaptic activity in Purkinje neurons by ATP

Adenosine triphosphate (ATP) is a versatile signalling molecule in the central and peripheral nervous system, where it can be released from both neurons and glial cells. In the cerebellum, ATP is released endogenously from the second postnatal week onwards, and is involved in the up-regulation of spontaneous synaptic input to Purkinje neurons by activation of purinergic P2 receptors. In the cerebellar cortex, ATP presumably acts on presynaptic inhibitory interneurons, which are excited by the activation of both P2X and P2Y receptors. P2 receptors have been reported for Purkinje neurons, where they mediate intracellular Ca2+ responses. The extracellular concentration of ATP is modulated by its enzymatic degradation by ecto-nucleotidases. Adenosine, which modulates evoked transmitter release, does not influence the spontaneous synaptic activity in Purkinje neurons. Some implications of ATP as a tonically active neuromodulator in the cerebellum are discussed.

[1]  G. Bernardi,et al.  Extracellular ATP and neurodegeneration. , 2003, Current drug targets. CNS and neurological disorders.

[2]  J. Deitmer,et al.  Purinergic modulation of synaptic input to Purkinje neurons in rat cerebellar brain slices , 2004, The European journal of neuroscience.

[3]  P. Illés,et al.  Neuronal P2 receptors of the central nervous system. , 2004, Current topics in medicinal chemistry.

[4]  J. Phillis.  Adenosine and adenine nucleotides as regulators of cerebral blood flow: roles of acidosis, cell swelling, and KATP channels. , 2004, Critical reviews in neurobiology.

[5]  A. Konnerth,et al.  Synaptic currents in cerebellar Purkinje cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. Fields,et al.  ATP: an extracellular signaling molecule between neurons and glia , 2000, Trends in Neurosciences.

[7]  E. Newman.  Glial modulation of synaptic transmission in the retina , 2004, Glia.

[8]  E. Castro,et al.  Ca 2 1 Signals Mediated by P 2 X-Type Purinoceptors in Cultured Cerebellar Purkinje Cells , 1998 .

[9]  E. Newman,et al.  Propagation of Intercellular Calcium Waves in Retinal Astrocytes and Müller Cells , 2001, The Journal of Neuroscience.

[10]  Geoffrey Burnstock,et al.  Electron-immunocytochemical localization of P2X1 receptors in the rat cerebellum , 1998, Cell and Tissue Research.

[11]  Alexander V. Gourine,et al.  ATP is a mediator of chemosensory transduction in the central nervous system , 2005, Nature.

[12]  Eric A Newman,et al.  Glial Cell Inhibition of Neurons by Release of ATP , 2003, The Journal of Neuroscience.

[13]  B. Fredholm,et al.  Adenosine receptors mediating inhibitory electrophysiological responses in rat hippocampus are different from receptors mediating cyclic AMP accumulation , 1984, Naunyn-Schmiedeberg's Archives of Pharmacology.

[14]  E. Shigetomi,et al.  ATP- and adenosine-mediated signaling in the central nervous system: synaptic purinoceptors: the stage for ATP to play its "dual-role". , 2004, Journal of pharmacological sciences.

[15]  M. Nedergaard,et al.  Cytoskeletal Assembly and ATP Release Regulate Astrocytic Calcium Signaling , 1998, The Journal of Neuroscience.

[16]  J. Deitmer,et al.  Enhancement of spontaneous synaptic activity in rat Purkinje neurones by ATP during development , 2005, The Journal of physiology.

[17]  P. Strata,et al.  Spontaneous electrical activity and dendritic spine size in mature cerebellar Purkinje cells , 2005, The European journal of neuroscience.

[18]  S. Kirischuk,et al.  Activation of P2-purino-,α1-adreno and H1-histamine receptors triggers cytoplasmic calcium signalling in cerebellar purkinje neurons , 1996, Neuroscience.

[19]  B. Fredholm,et al.  Actions of adenosine at its receptors in the CNS: insights from knockouts and drugs. , 2005, Annual review of pharmacology and toxicology.

[20]  E. Castro,et al.  Ca2+ Signals Mediated by P2X-Type Purinoceptors in Cultured Cerebellar Purkinje Cells , 1998, The Journal of Neuroscience.

[21]  D. Prince,et al.  Adenosine decreases neurotransmitter release at central synapses. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[22]  G. Burnstock,et al.  Expression of P2X purinoceptors during rat brain development and their inhibitory role on motor axon outgrowth in neural tube explant cultures , 2005, Neuroscience.

[23]  M. O'regan.  Adenosine and the regulation of cerebral blood flow , 2005, Neurological research.

[24]  H Zimmermann,et al.  New insights into molecular structure and function of ecto-nucleotidases in the nervous system , 1998, Neurochemistry International.

[25]  Y. Ehrlich,et al.  Ecto-protein kinases as mediators for the action of secreted ATP in the brain. , 1999, Progress in brain research.

[26]  B S Khakh,et al.  International union of pharmacology. XXIV. Current status of the nomenclature and properties of P2X receptors and their subunits. , 2001, Pharmacological reviews.

[27]  M. Rubio,et al.  Distinct Localization of P2X Receptors at Excitatory Postsynaptic Specializations , 2001, The Journal of Neuroscience.

[28]  M. Ikekita,et al.  Neuroprotective effect of adenine on purkinje cell survival in rat cerebellar primary cultures , 2003, Journal of neuroscience research.

[29]  G. Burnstock,et al.  Cellular distribution and functions of P2 receptor subtypes in different systems. , 2004, International review of cytology.

[30]  Eric A Newman,et al.  Calcium Increases in Retinal Glial Cells Evoked by Light-Induced Neuronal Activity , 2005, The Journal of Neuroscience.

[31]  Mu-ming Poo,et al.  ATP Released by Astrocytes Mediates Glutamatergic Activity-Dependent Heterosynaptic Suppression , 2003, Neuron.

[32]  J. Deitmer,et al.  Long‐lasting modulation of synaptic input to Purkinje neurons by Bergmann glia stimulation in rat brain slices , 2002, The Journal of physiology.

[33]  G Burnstock,et al.  Receptors for purines and pyrimidines. , 1998, Pharmacological reviews.

[34]  G. Housley,et al.  Localization of ATP-gated ion channels in cerebellum using P2x2R subunit-specific antisera. , 1996, Neuroreport.

[35]  WG Regehr,et al.  Contributions of calcium-dependent and calcium-independent mechanisms to presynaptic inhibition at a cerebellar synapse , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  T. Takano,et al.  Intercellular calcium signaling mediated by point-source burst release of ATP , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Marta Garcı́a-Lecea,et al.  P2X2 characteristics of the ATP receptor coupled to [Ca2+] i increases in cultured Purkinje neurons from neonatal rat cerebellum , 1999, Neuropharmacology.