Effect of kainate on the membrane conductance of hilar glial precursor cells recorded in the perforated-patch configuration.

The effects of kainate on membrane current and membrane conductance were investigated in presumed hilar glial precursor cells of juvenile rats. The perforated-patch configuration was used also to reveal possible second-messenger effects. Kainate evoked an inward current that was accompanied by a biphasic change in membrane conductance in 69% of the cells. An initial conductance increase with a time course similar to that of the inward current was followed by a second delayed conductance increase. This second conductance was absent in whole-cell-clamp recordings, suggesting that it was mediated by a second messenger effect. Analysis of the reversal potentials of the membrane current during both phases of the kainate-induced conductance change revealed that the first conductance increase reflected the activation of AMPA receptors. Several lines of evidence suggest that the delayed second conductance increase was due to the indirect activation of Ca2+-dependent K+ channels via Ca2+-influx through AMPA receptors. (1) the delayed second conductance increase was blocked by Ba2+ and the reversal of its underlying current was significantly shifted towards EK+, suggesting that it is due to the activation of K+ channels. (2) The delayed second conductance increase disappeared in a Ca2+-free saline buffered with BAPTA, indicating that it depended on Ca2+-influx. (3) Co2+, Cd2+ and nimodipine failed to block the delayed second conductance increase excluding a major contribution of voltage-dependent Ca2+ channels. (4) The involvement of metabotropic glutamate receptors also appeared unlikely, because the kainate-induced delayed second conductance increase could not be blocked by a depletion of the intracellular Ca2+ stores with the Ca2+-ATPase inhibitor thapsigargin, and t-ACPD exerted no effect on membrane current and conductance. We conclude that kainate activates directly AMPA receptors in presumed hilar glial precursor cells. This results in a Ca2+ influx that could lead indirectly to the activation of Ca2+-dependent K+ channels.