Adenosine decreases neurotransmitter release at central synapses.
Adenosine, at concentrations ranging from 5 to 100 microM, decreases the efficacy of transmission at the perforant path synapses on dentate granule cells. We have used whole cell recording from these cells in slices to determine the mechanism of the reduced synaptic strength. We find that size of miniature excitatory postsynaptic currents (mepscs) is unaffected by adenosine at concentrations up to 100 microM, an observation that indicates adenosine's mode of action is not through a decreased postsynaptic sensitivity to neurotransmitter. A quantal analysis indicates, however, that the quantity of neurotransmitter released is sufficiently diminished by adenosine to account entirely for the adenosine-produced decrease in synaptic strength. Application of 3-isobutyl-1-methylxanthine (IBMX), a drug that antagonizes the effects of endogenous adenosine, produces an increase in synaptic strength. This observation suggests that the resting level of adenosine in our slices is appreciable, and an analysis of the adenosine dose-response relation is consistent with endogenous adenosine levels of about 10 microM. IBMX application produces only slight changes in the amplitude of mepscs, whereas a quantal analysis demonstrates that the drug significantly increases the amount of neurotransmitter released. Thus IBMX acts as an "anti-adenosine" in our experiments. In some experiments we have been able to record excitatory and inhibitory synaptic currents produced by the same perforant path stimulus. In these instances we find that inhibitory transmission is unaffected by concentrations of adenosine that produce a marked decrease in the strength of excitatory synapses.
Prince
D A
DA
Salk Institute, La Jolla, CA 92037.
Stevens
C F
CF
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine