Diapositive 1

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Synaptic corelease of ATP and GABA in cultured
spinal neurons
Young-Hawan Jo and Rémy Schlichter Laboratoire
de Neurophysiologie cellulaire et intégrée, UMR
7519 CNRS, Université Louis Pasteur, 21 rue
Descartes, Strasbourg, France
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Introduction
Methodology
Results
Discussion
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Introduction
Methodology
Results
Discussion
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Introduction
Methodology
Results
Discussion

• Ad C ? Glutamate Subtance P (fast and slow)

• Local interneurons ? Glut ou GABA

Inputs

• Electrical stimulation of Iaire afferent ? ATP
  release in superficial Dorsal Horn by local
  interneurons (Sawynok Downie, 1993, Brain
  research)

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Introduction
Methodology
Results
Discussion

• Expression mRNAs that coding for P2X2, P2X4,
  P2X6 subunits in Lamina I and II (Collo, 1996, J.
  Neuroscience)

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Introduction
Methodology
Results
Discussion
ATP may serve as a fast neurotransmitter between
superficial dorsal horn neurons?
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10d
Cultured spinal dorsal horn neurons
Perforated patch-clamp
IPSP or EPSP
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Coreleased ATP-GABA
Interaction ATP-GABA
AP-5 CNQX Bicuculine Strychnine BSCA
Inward currents EPSPs
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Coreleased ATP-GABA
Interaction ATP-GABA
Suramine ou PPADS
Release of ATP acts on P2X Rr
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Coreleased ATP-GABA
Interaction ATP-GABA
Differents threshold
Reversal potential 0 mV ? nonselective cation
conductance
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Coreleased ATP-GABA
Interaction ATP-GABA
K
Ca2
Na
Reversal potential 0mV
EPSPs
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Interaction ATP-GABA
EPSPc
No EPSPc
  Wash-out CNQX and AP-5 Wash-out bicuculine
No EPSPs under BSCA Yes Yes
EPSPs under BSCA No Yes
? EPSP
BSCA
gt ATP is coreleased with GABA
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Interaction ATP-GABA
Glutamate
No ATP
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Interaction ATP-GABA

• If Em Ex ? ions flux 0

• ECl -90mV
• Ecations 0 mV

gt 70 of GABAergic synapse corelease ATP
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Interaction ATP-GABA
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Interaction ATP-GABA
70
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spontaneous liberation of GABA and no ATP
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Interaction ATP-GABA
Post
Degradation of ATP (metabolite) inhibs IPSP cause
by isoguvacine
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Interaction ATP-GABA
Post
ATP ? Adenosine ? Inhibs GABA IPSP
Adenosine Rr
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Interaction ATP-GABA
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Interaction ATP-GABA
GABA
5 nucléotidase
-
P2X Rr
GABA Rr
Adenosine Rr
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• Result are in accord with the fact that P2X
  receptor mediated excitatory synaptic
  transmission in 50 of neurons in DH ? ATP is a
  prominent NT
• ATP is coreleased with GABA
• In vivo ? they dont find corealesed of ATP and
  GABA
• Important because it doesnt imply a circuitry
  to modulate response
• Can have implication in a hyperalgesia (repeated
  stimulation)

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Thank you for your attention
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