Synaptic corelease of ATP and GABA in cultured spinal neurons

Nat Neurosci. 1999 Mar;2(3):241-5. doi: 10.1038/6344.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Cells, Cultured
  • Electric Conductivity
  • Neural Inhibition / physiology
  • Neurons / metabolism
  • Rats
  • Receptors, GABA-A / physiology
  • Receptors, Neurotransmitter / physiology
  • Receptors, Purinergic P2* / physiology
  • Spinal Cord / cytology
  • Spinal Cord / metabolism*
  • Synapses / metabolism*
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / metabolism*


  • Receptors, GABA-A
  • Receptors, Neurotransmitter
  • Receptors, Purinergic P2
  • gamma-Aminobutyric Acid
  • Adenosine Triphosphate