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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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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