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γ‐Aminobutyric acid A receptor subunit expression predicts functional changes in hippocampal dentate granule cells during postnatal development
Author(s) -
BrooksKayal Amy R.,
Shumate Melissa D.,
Jin Hong,
Rikhter Tatiana Y.,
Kelly Mary Ellen,
Coulter Douglas A.
Publication year - 2001
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 - 10.1046/j.1471-4159.2001.00329.x
Subject(s) - dentate gyrus , hippocampal formation , biology , gabaergic , receptor , endocrinology , protein subunit , medicine , gabaa receptor , granule cell , receptor expression , gabaa rho receptor , gaba receptor , neuroscience , microbiology and biotechnology , biochemistry , gene
Profound alterations in the function of GABA occur over the course of postnatal development. Changes in GABA A receptor expression are thought to contribute to these differences in GABAergic function, but how subunit changes correlate with receptor function in individual developing neurons has not been defined precisely. In the current study, we correlate expression of 14 different GABA A receptor subunit mRNAs with changes in the pharmacological properties of the receptor in individual hippocampal dentate granule cells over the course of postnatal development in rat. We demonstrate significant developmental differences in GABA A receptor subunit mRNA expression, including greater than two‐fold lower expression of α1‐, α4‐ and γ2‐subunit mRNAs and 10‐fold higher expression of α5‐mRNA in immature compared with adult neurons. These differences correlate both with regional changes in subunit protein level and with alterations in GABA A receptor function in immature dentate granule cells, including two‐fold higher blockade by zinc and three‐fold lower augmentation by type‐I benzodiazepine site modulators. Further, we find an inverse correlation between changes in GABA A receptor zinc sensitivity and abundance of vesicular zinc in dentate gyrus during postnatal development. These findings suggest that developmental differences in subunit expression contribute to alterations in GABA A receptor function during postnatal development.