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Synaptic Co-Release of ATP and GABA

Functional Characteristics, Modulation and Physiological Implications

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Co-Existence and Co-Release of Classical Neurotransmitters

Abstract

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.

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Abbreviations

ACh:

Acetylcholine

ADP:

adenosine 5’-diphosphate

AMP:

adenosine 5’-monophosphate

ATP:

adenosine 5’-triphosphate

CNQX:

6-cyano-7-nitroquinoxaline-2,3-dione

D-APV:

D-amino-phosphonovaleric acid

ECl :

equilibrium potential for Cl- ions

Ecations :

equilibrium potential for cations

ePSC:

electrically-evoked postsynaptic current

eEPSC:

electrically-evoked excitatory postsynaptic current

eIPSC:

electrically-evoked inhibitory postsynaptic current

DHEA:

dehydroepiandrosterone

DPCPX:

8-Cyclopentyl-1,3-dipropylxanthine

GABA:

γ-aminobutyric acid

HP:

holding potential

mPSC:

miniature postsynaptic current

mEPSC:

miniature excitatory postsynaptic current

mIPSC:

miniature inhibitory postsynaptic current

NA:

noradrenaline

NMDA:

N-methyl-D-Aspartic acid

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Acknowledgments

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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Authors and Affiliations

  1. Université Louis Pasteur, Institut des Neurosciences Cellulaires et Intégratives (INCI), Centre National de la Recherche Scientifique (CNRS), UMR7168, F-67084, Strasbourg, France

    R. Schlichter

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  1. S. Hugel
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  2. Y.H. Jo
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  3. R. Schlichter
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Correspondence to R. Schlichter .

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  1. Centro de Investigación y de, Estudios Avanzados, Instituto Politécnico Nacional, Mexico, 07000, Mexico

    Rafael Gutierrez

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Hugel, S., Jo, Y., Schlichter, R. (2009). Synaptic Co-Release of ATP and GABA. In: Gutierrez, R. (eds) Co-Existence and Co-Release of Classical Neurotransmitters. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-09622-3_11

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