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Synaptic corelease of ATP and GABA in cultured spinal neurons

Abstract

In the spinal dorsal horn (DH), transmission and modulation of peripheral nociceptive (pain-inducing) messages involve classical neurotransmitters and neuropeptides. We show that approximately half of DH neurons use ATP as a fast excitatory neurotransmitter acting at ionotropic P2X postsynaptic receptors. ATP was not codetected with glutamate but was coreleased with the inhibitory neurotransmitter GABA. Moreover, adenosine, probably generated by extracellular metabolism of ATP, finely tuned GABAergic inhibitory postsynaptic currents. Differential modulation of excitatory versus inhibitory components of this mixed cotransmission may help to explain changes in sensory message processing in the DH during mechanical hyperalgesia and neuropathic pain.

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Figure 1: Properties of ATP (P2X) receptor-mediated EPSCs in DH neurons.
Figure 2: Synaptic corelease of ATP and GABA.
Figure 3: ATP and GABA are coreleased from a single presynaptic neuron.
Figure 4: ATP is degraded to adenosine and inhibits GABAA-receptor-mediated currents in DH neurons.
Figure 5: ATP coreleased with GABA is probably degraded into adenosine and inhibits GABAergic IPSCs.

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Acknowledgements

We thank Catherine Moreau and Madeleine Roth for technical assistance and Sylvain Hugel for help with some of the experiments. This work was supported by a grant from the UPSA Pain Institute. We acknowledge further support from the Université Louis Pasteur and the Centre National de la Recherche Scientifique (CNRS).

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Correspondence to Rémy Schlichter.

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Jo, YH., Schlichter, R. Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat Neurosci 2, 241–245 (1999). https://doi.org/10.1038/6344

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