Day-night variations in zinc sensitivity of GABAA receptor-channels in rat suprachiasmatic nucleus.
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 gamma-aminobutyric acid (GABA)-ergic neurons, it is unknown whether there are circadian changes in the GABAA receptor expression and/or function. Here we investigated the possible daily variations in zinc sensitivity of GABAA 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 microM GABA were inhibited by Zn2+ with an IC50 of 50.3+/-3.2 microM, whereas currents evoked by 100 microM GABA were inhibited with an IC50 of 181.6+/-32.0 microM. The antagonist action of zinc saturated at 97.4+/-0.7% for 30 microM GABA and 91.6+/-2.7% for 100 microM GABA. These observations indicate that Zn2+ inhibits SCN GABAA 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 IC50 for zinc was significantly lower than during the night (43.9+/-4.7 microM vs. 58.6+/-3.8, respectively). These results indicate that native GABAA receptors in SCN neurons display pharmacological properties of receptors having and not having gamma subunit and that the proportionality of these receptors could change during the day and night.
Kretschmannova
Karla
K
Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic.
Svobodova
Irena
I
Zemkova
Hana
H
D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018756:GABA Antagonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D015032:Zinc; D001640:Bicuculline