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GABA Alters GABA A Receptor mRNAs and Increases Ligand Binding
Author(s) -
Kim Helen Y.,
Sapp Douglas W.,
Olsen Richard W.,
Tobin Allan J.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb07481.x
Subject(s) - bicuculline , cerebellum , gabaa receptor , receptor , gaba receptor , gabab receptor , agonist , gaba receptor antagonist , inhibitory postsynaptic potential , gamma aminobutyric acid , neurotransmitter , chemistry , biology , microbiology and biotechnology , granule (geology) , neuroscience , biochemistry , paleontology
In addition to its role as an inhibitory neurotransmitter, γ ‐aminobutyric acid (GABA) influences the cytodifferentiation of developing neurons both in culture and in vivo. Here, we report some of the targets of GABA action and the mechanism through which GABA acts. In primary cultures of cerebellar granule cells, GABA specifically stimulates an increase in the levels of mRNAs for α 1 and β 2 GABA A receptor subunits. The GABA A agonist 4, 5, 6, 7‐tetrahydroisoxazolo [5, 4‐c]pyridin‐3‐ol (THIP) mimics this effect, and the GABA A antagonist bicuculline prevents it. In addition, GABA and THIP trigger an increase in the number of GABA binding sites. This increase parallels that seen in vivo, where the total number of GABA A receptor sites increases during postnatal cerebellar development. It is interesting that the period of the greatest increase in the number of receptor sites coincides with the development of the granule cells. Taken together, our data suggest that GABA may play an important role during maturation of cerebellar granule cells by influencing the number and composition of its own receptors.