Activity-dependent release of adenosine contributes to short-term depression at CA3-CA1 synapses in rat hippocampus.
High-frequency stimulation results in a transient, presynaptically mediated decrease in synaptic efficacy called short-term depression (STD). Stimulation of Schaffer-collateral axons at 10 Hz for 5 s resulted in approximately 75% depression of excitatory postsynaptic current (EPSC) slope recorded from CA1 cells in rat organotypic slice cultures. An adenosine A(1) receptor antagonist decreased the magnitude of STD elicited with 10-Hz stimulation by approximately 30%. The A(1) receptor antagonist had no effect on STD elicited with 3-Hz stimulation. The activation of A(1) receptors during 10-Hz stimulation was not due to the extracellular conversion of released ATP to adenosine, because block of 5'-ectonucleotidases did not significantly affect STD. The adenosine transport inhibitor dipyridamole did not reduce STD, indicating that adenosine was not released by facilitated transport. We conclude that 10-Hz, but not 3-Hz, stimulation causes the vesicular release of adenosine and the rapid (<3 s) activation of presynaptic inhibitory A(1) receptors, which account for approximately 40% of homosynaptic EPSC depression.
Brager
Darrin H
DH
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA. dbrag001@umaryland.edu
Thompson
Scott M
SM
D000241:Adenosine / Q000378:metabolism*; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine