Inhibition of GABAA ligand-gated Cl- channels by zinc in adult rat brain: a regional study.

Abstract:

:Zinc (Zn2+) was shown to invariably inhibit muscimol-stimulated 36Cl- uptake by synaptoneurosomes in the cerebral cortex, hippocampus and cerebellum. The Zn2+ sensitivity of the GABAA receptor-gated 36Cl- uptake in the cerebral cortex was comparable to that in the hippocampus, whereas the uptake in the cerebellum was less sensitive to Zn2+. Although diazepam-potentiation of muscimol-stimulated 36Cl- uptake was unaltered by 100 microM Zn2+ in the cerebral cortex and hippocampus, diazepam caused no enhancement in the presence of Zn2+ in the cerebellum. Zn2+ inhibited [3H]diazepam binding significantly at 1 mM in the cerebral cortex and cerebellum, whereas Ni2+ increased the binding in a concentration-dependent manner in both regions. Although lower concentrations of Zn2+ did not affect [3H]Ro 15-4513 binding to diazepam-sensitive sites, higher concentrations of ZN2+ increased the binding in both regions. Unlike the diazepam-sensitive sites, the diazepam-insensitive [3H]Ro 15-4513 binding was not affected by Zn2+ or Ni2+ at any of the tested concentrations. These results suggest that the GABAA ligand-gated Cl- flux and its diazepam-potentiation are heterogeneously modulated in various brain regions. It is also suggested that cerebellar diazepam-insensitive [3H]Ro 15-4513 binding sites are insensitive to Zn2+ and Ni2+.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Ito Y,Segawa K,Kobayashi M,Fukuda H

doi

10.1007/BF02532346

subject

Has Abstract

pub_date

1996-08-01 00:00:00

pages

955-61

issue

8

eissn

0364-3190

issn

1573-6903

journal_volume

21

pub_type

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