Day-night variations in zinc sensitivity of GABAA receptor-channels in rat suprachiasmatic nucleus

Abstract In the suprachiasmatic nucleus (SCN), electrical activity, secretion, and other cellular functions undergo profound rhythm during day–night cycle due to oscillatory expression of clock gene constituents. Although SCN is enriched with γ-aminobutyric acid (GABA)-ergic neurons, it is unknown whether there are circadian changes in the GABA A receptor expression and/or function. Here we investigated the possible daily variations in zinc sensitivity of GABA A channels in rat SCN neurons maintained in brain slices. Extracellular zinc inhibited GABA-induced currents in all ventrolateral (VL) and dorsomedial (DM) SCN neurons studied, as well as in neurons of non-SCN regions. In SCN neurons, the currents evoked by 30 μM GABA were inhibited by Zn 2+ with an IC 50 of 50.3±3.2 μM, whereas currents evoked by 100 μM GABA were inhibited with an IC 50 of 181.6±32.0 μM. The antagonist action of zinc saturated at 97.4±0.7% for 30 μM GABA and 91.6±2.7% for 100 μM GABA. These observations indicate that Zn 2+ inhibits SCN GABA A receptor competitively and in part non-competitively. In SCN neurons, but not in other neurons, the zinc sensitivity varied with daily time. During the day, the calculated IC 50 for zinc was significantly lower than during the night (43.9±4.7 μM vs. 58.6±3.8, respectively). These results indicate that native GABA A receptors in SCN neurons display pharmacological properties of receptors having and not having γ subunit and that the proportionality of these receptors could change during the day and night.