Synaptic Co-Release of ATP and GABA

Functional Characteristics, Modulation and Physiological Implications
  • S. Hugel
  • Y.H. Jo
  • R. Schlichter


Over the last 30 years, adenosine 5’-triphosphate (ATP) has been clearly established as a cotransmitter with noradrenaline and acetylcholine in the peripheral nervous system. More recently, ATP was also identified as a cotransmitter in the central nervous system. In neuronal cultures from postnatal rat spinal cord dorsal horn or embryonic chick and postnatal mouse lateral hypothalamus, ATP was surprisingly found to be synaptically coreleased with the inhibitory neurotransmitter GABA, but not with glutamate. In these preparations, ATP activates excitatory cation-permeable receptors (P2X receptors), whereas GABA stimulates anion-permeable inhibitory GABAA receptors. The corelease of ATP and GABA therefore results in a fast mixed excitatory/inhibitory ATP/GABA cotransmission. Here we review the current knowledge on ATP/GABA cotransmission, the possible interactions of synaptically released ATP and GABA at pre- and postsynaptic sites and discuss the issues related to the role of this mixed cotransmission in the context of physiological and pathological situations.


Dorsal Horn GABAA Receptor Synaptic Cleft GABAB Receptor Lateral Hypothalamus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of abbreviations




adenosine 5’-diphosphate


adenosine 5’-monophosphate


adenosine 5’-triphosphate




D-amino-phosphonovaleric acid


equilibrium potential for Cl- ions


equilibrium potential for cations


electrically-evoked postsynaptic current


electrically-evoked excitatory postsynaptic current


electrically-evoked inhibitory postsynaptic current






γ-aminobutyric acid


holding potential


miniature postsynaptic current


miniature excitatory postsynaptic current


miniature inhibitory postsynaptic current




N-methyl-D-Aspartic acid



The authors would like to acknowledge financial support from Centre National de la Recherche Scientifique (CNRS), French Ministry of Education and Research, University Louis Pasteur, Institut UPSA de la Douleur, DRTC and American Diabetes Association.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Université Louis Pasteur, Institut des Neurosciences Cellulaires et Intégratives (INCI), Centre National de la Recherche Scientifique (CNRS)F-67084France

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