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ATP receptor-mediated synaptic currents in the central nervous system
F A Edwards1, A J Gibb, D Colquhoun
1Department of Pharmacology, University College London, UK.
Nature
|September 10, 1992
Summary
Adenosine 5'-triphosphate (ATP) is now recognized as a fast excitatory neurotransmitter in the brain. This study provides the first direct evidence of ATP-mediated synaptic currents in the central nervous system.
Area of Science:
- Neuroscience
- Neurophysiology
- Molecular Biology
Background:
- Glutamate has been the sole established fast excitatory neurotransmitter in the brain.
- Adenosine 5 -triphosphate (ATP) has known roles in the peripheral nervous system, but its function as a central nervous system neurotransmitter remained unproven.
Purpose of the Study:
- To investigate the potential role of ATP as a fast excitatory neurotransmitter in the mammalian brain.
- To identify the specific receptors mediating synaptic currents in the rat medial habenula.
Main Methods:
- Recording of evoked and miniature synaptic currents in rat medial habenula slices.
- Utilizing receptor blockers (suramin) and agonists (alpha,beta-methylene-ATP) to identify neurotransmitter involvement.
- Testing the effects of glutamate, gamma-aminobutyric acid, and acetylcholine receptor blockers.
Main Results:
- Synaptic currents with fast rise times, indicative of ligand-gated ion channels, were recorded.
- These currents were insensitive to glutamate, gamma-aminobutyric acid, and acetylcholine receptor blockers.
- Crucially, the currents were blocked by suramin and alpha,beta-methylene-ATP, implicating ATP receptors.
Conclusions:
- This study provides the first direct evidence for synaptic currents in the brain mediated by adenosine 5 -triphosphate receptors.
- ATP functions as a fast excitatory neurotransmitter in the central nervous system, specifically in the medial habenula.
- These findings expand our understanding of neurotransmission in the brain.
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