Abstract
Although ATP is reported to modulate synaptic plasticity, the mechanism of action of ATP on synaptic transmission is not fully understood. Here we show that ATP enhances long-term potentiation (LTP), and P2X receptor antagonists inhibit this ATP effect, but do not affect paired pulse facilitation (PPF) in rat hippocampal slices. ATP rapidly increases intracellular calcium, and P2X receptor antagonists inhibit this increase in cultured dissociated neurons. These results indicate that ATP enhances LTP via activation of postsynaptic P2X receptors. A pertussis toxin-sensitive G-protein inhibitor significantly attenuates PPF, although it does not affect LTP, indicating that presynaptic P2Y receptors also play an important role in neuronal plasticity. We conclude that ATP modulates synaptic plasticity via dual effects on pre- and post-synaptic mechanisms.
MeSH terms
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Adenosine Triphosphate / metabolism
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Adenosine Triphosphate / pharmacology*
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Animals
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Animals, Newborn
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Calcium / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / physiology
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Electric Stimulation
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GTP-Binding Proteins / antagonists & inhibitors
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GTP-Binding Proteins / metabolism
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Hippocampus / cytology
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Hippocampus / drug effects
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Hippocampus / metabolism*
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In Vitro Techniques
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology*
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Neural Pathways / cytology
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Neural Pathways / drug effects
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Neural Pathways / metabolism
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism
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Purinergic P2 Receptor Agonists
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Purinergic P2 Receptor Antagonists
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Rats
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Rats, Sprague-Dawley
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Receptors, Purinergic P2 / metabolism*
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Receptors, Purinergic P2X
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Synaptic Membranes / drug effects
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Synaptic Membranes / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
Substances
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Purinergic P2 Receptor Agonists
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Purinergic P2 Receptor Antagonists
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Receptors, Purinergic P2
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Receptors, Purinergic P2X
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Adenosine Triphosphate
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GTP-Binding Proteins
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Calcium