Postsynaptic inhibition by adenosine in hippocampal CA3 neurons: Co2+-sensitive activation of an inwardly rectifying K+ conductance

The properties of the current underlying the membrane hyperpolarization evoked by adenosine (50–100 m) were investigated in hippocampal CA3 neurons in vitro using current-clamp and single-electrode voltage-clamp techniques. In voltage-clamp measurements, the adenosine-induced current (I_Ado) was outward at rest and reversed at membrane potentials close to the equilibrium potential of K⁺ (E_K), indicating that I_Ado was carried by K⁺ ions. Determination of I_Ado at several membrane potentials revealed a nonlinear current/voltage (I/V) relationship of the current displaying inward rectification in the hyperpolarizing direction. Similarly, adenosine increased the membrane slope conductance only at membrane potentials negative to rest, whereas the slope of the neuronal I/V curve remained unchanged when determined at potentials positive to rest. Since the electrophysiological properties of I_Ado were very similar to those described for K⁺ conductances activated by other neuroactive substances like serotonin, opioid peptides and -aminobutyric acid B receptor (GABA_B) agonists, we conclude that I_Ado belongs to a family of ligand-operated, inwardly rectifying K⁺ currents which apparently share a common mechanism to reduce postsynaptic excitability. As an additional feature, the postsynaptic adenosine response was reduced by bath application of Co²⁺ or Ni²⁺. The adenosine-induced membrane hyperpolarization was not affected by low-Ca²⁺ or low-Mg²⁺ solutions, nor by buffering of intra-cellular Ca²⁺, but a gradual decline of I_Ado was observed following superfusion with Co²⁺ or Ni²⁺. In contrast, Mn²⁺ caused only a weak attenuation of the adenosine response.