Alpha subunits influence Zn block of gamma 2 containing GABAA receptor currents.
The two-electrode voltage-clamp technique was used to evaluate Zn block of current activated by gamma-aminobutyric acid (GABA) in Xenopus oocytes injected with cRNA coding for alpha 1 beta 3 gamma 2, alpha 2 beta 3 gamma 2, or alpha 3 beta 3 gamma 2 subunits of the GABAA receptor (GABAAR). cDNA coded for the human form of alpha 1, alpha 2, beta 3 and gamma 2L subunits. alpha 3 subunit cDNA was obtained from an African green monkey library. Zn significantly inhibited the current evoked by application of GABA. Maximal inhibition was greater in alpha 2- and alpha 3- containing GABAARs than in alpha 1-containing GABAARs (51 +/- 1% and 53 +/- 2% vs 19 +/- 2%, respectively). The IC50 for Zn was smaller in alpha 1 than in alpha 2 or alpha 3 GABAARs (1.2 +/- 0.3 microM vs 7 +/- 1 and 9 +/- 1 microM, respectively). Zn shifted the concentration-response curve of GABA to the right in a parallel manner. These data suggest that Zn reduces the amplitude of current evoked at gamma 2 subunit containing GABAARs through an allosteric mechanism.
White
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Neurogen Corporation, Branford, CT 06405, USA.
Gurley
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DA
D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D009865:Oocytes; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000187:drug effects*; D014982:Xenopus laevis; D015032:Zinc / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D015032:Zinc; D000525:Alprazolam