Adenosine inhibits evoked synaptic transmission primarily by reducing presynaptic calcium influx in area CA1 of hippocampus.
Adenosine is a potent modulator of neuronal activity throughout the nervous system. Previous evidence suggests that adenosine presynaptically inhibits synaptic transmission. The mechanism of presynaptic inhibition is uncertain. Adenosine may inhibit transmitter release by reducing voltage-dependent Ca2+ currents, activating K+ currents, or by mechanisms downstream to Ca2+ influx. By simultaneously recording the presynaptic Ca2+ transient ([Ca]t) and the field excitatory postsynaptic potential (fEPSP) at CA3-CA1 synapses of hippocampal slices, we found that adenosine, through activation of presynaptic A1 receptors, inhibits the fEPSP primarily by reducing the [Ca]t. Reduced [Ca]t was due to inhibition of omega-conotoxin GVIA-sensitive and some unidentified Ca2+ channels, probably including Q-type, but not to omega-agatoxin-IVA-sensitive Ca2+ channels. The adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine enhanced both the [Ca]t and the fEPSP, suggesting a tonic inhibition of the [Ca]t by endogenous adenosine in the hippocampal slice.
Wu
L G
LG
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.
Saggau
P
P
D000241:Adenosine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D010455:Peptides / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D010455:Peptides; D018047:Receptors, Purinergic P1; D014970:Xanthines; D020866:omega-Conotoxin GVIA; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D002118:Calcium