A1 adenosine receptors differentially regulate the N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor-mediated components of hippocampal excitatory postsynaptic current in a Ca2+/Mg(2+)-dependent manner.

A1 adenosine receptors efficiently modulate the excitatory synaptic transmission in hippocampus. Here we report that in addition to previously known modulatory action on the synaptic efficacy, A1 adenosine receptors are also capable of regulating the relative contribution of N-methyl-D-aspartate receptor-mediated component of the excitatory postsynaptic current in CA3-CA1 excitatory synapses, in the rat. When applied externally, a selective A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine, increases not only the amplitude of excitatory postsynaptic current but also the relative contribution of the N-methyl-D-aspartate receptor-mediated component of postsynaptic current recorded by in situ voltage clamp. This effect develops only at increased external Ca2+ concentration and also depends on the external Ca2+/Mg2+ ratio. The increased ratio of N-methyl-D-aspartate/non-N-methyl-D-aspartate components of excitatory postsynaptic current remains at a new level after the removal of 8-cyclopentyl-1,3-dimethylxanthine, even though the amplitude of excitatory postsynaptic current returns close to control value. These results indicate the existence of a mechanism that preferentially enhances the N-methyl-D-aspartate component of excitatory postsynaptic current when the A1 adenosine receptors are blocked and imprints the newly acquired ratio of corresponding excitatory postsynaptic current components.