OPIOID INHIBITION OF HIPPOCAMPAL INTERNEURONS VIA MODULATION OF POTASSIUM AND HYPERPOLARIZATION-ACTIVATED CATION (I-H) CURRENTS

The actions of mu- and delta-opioid agonists (DAMGO and DPDPE, respect ively) on GABAergic interneurons in stratum oriens of area CA1 of the hippocampus were examined by using whole-cell voltage-clamp recordings in brain slices. Both agonists consistently generated outward current s of similar magnitude (15-20 pA) in the majority of cells. However, u nder control conditions, current-voltage (I/V) relationships revealed that only a small number of these cells (3 of 77) demonstrated clear i ncreases in membrane conductance, associated with the activation of th e potassium current known as G(irk). These interneurons also exhibited a slowly activating, inwardly rectifying current known as I-h on hype rpolarizing step commands. I-h was blocked by the extracellular applic ation of cesium (3-9 mM) or ZD 7288 (10-100 mu M) but was insensitive to barium (1-2 mM). In an effort to determine whether the holding curr ent changes were attributable to the modulation of G(irk) and/or I-h, we used known blockers of these ion channels (barium or cesium and ZD 7288, respectively). Extracellular application of cesium (3-9 mM) or Z D 7288 (25-100 mu M) blocked I-h and significantly reduced the opioid- induced outward currents by 58%. Under these conditions the opioid ago nists activated a potassium current with characteristics similar to G( irk). Similarly, during barium (1-2 mM) application the opioid-induced outward currents were reduced by 46%, and a clear reduction in I-h an d the whole-cell conductance was revealed. These data suggest that the opioids can modulate both I-h and G(irk) in the same population of st ratum oriens interneurons and that the modulation of these ion channel s can contribute to the inhibition of interneuron activity in the hipp ocampus.