Interaction between adenosine and GABAA receptors on hippocampal neurones

Extracellular recordings were made from the CA1 pyramidal cell layer of hippocampal slices in response to stimulation of Schaffer collateral fibres in stratum radiatum. Adenosine and muscimol induced concentration-dependent reductions in the amplitude of orthodromically induced population potentials. In order to eliminate effects of these agents on potassium channels, experiments were performed in the presence of barium, 1 mM. This concentration increased potential size, and reduced the inhibitory effect of adenosine on population spike size, but not synaptic potential size. This profile is consistent with the blockade of potassium channels associated only with the postsynaptic effects of adenosine. Muscimol responses were unaffected. Adenosine potentiated the ability of muscimol to inhibit evoked potentials in the absence or presence of barium. The potentiation was prevented by the A1 selective antagonist 8-cyclopentyltheophylline. The effects of adenosine as well as muscimol were reduced by the chloride channel blockers DIDS, which also prevented the adenosine potentiation of muscimol. The results indicate the ability of adenosine to operate chloride channels in hippocampal neurones, and suggest a potentiative interaction between adenosine and muscimol which may also involve chloride channels.