Premium
The effect of GABA stimulation on GABA A receptor subunit protein and mRNA expression in rat cultured cerebellar granule cells
Author(s) -
Piatt Kathleen P.,
Zwartjes Raymond E.,
Bristow David R.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16051.x
Subject(s) - protein subunit , medicine , gabaa receptor , endocrinology , messenger rna , biology , stimulation , receptor , cerebellum , microbiology and biotechnology , biochemistry , gene
1 After 8 days in vitro , rat cerebellar granule cells were exposed to 1 mM γ‐aminobutyric acid (GABA) for periods of 1, 2, 4, 6, 8 and 10 days. The effect of the GABA exposure on GABA A receptor al, a6 and β2,3 subunit protein expression and α1 and α6 subunit steady‐state mRNA levels, was examined using Western blotting and reverse transcriptase‐polymerase chain reaction (RT‐PCR), respectively. 2 GABA exposure for 2 days decreased α1 (35 ± 10%, mean ± s.e.mean), β2,3 (21±9%) and α6 (28 ± 10%) subunit protein expression compared to control levels. The GABA‐mediated reduction in al subunit expression after 2 days treatment was abolished in the presence of the GABA A receptor antagonist, Ru 5135 (10 μ m ). 3 GABA exposure for 8 days increased α1 (26 ± 10%, mean ± s.e.mean) and β2,3 (56 ± 23%) subunit protein expression over control levels, whereas α6 subunit protein expression remained below control levels (by 38 ± 10%). However, after 10 days GABA exposure, a6 subunit protein expression was also increased over control levels by 65 ± 29% (mean ± s.e.mean). 4 GABA exposure did not change the α1 or α6 subunit steady‐state mRNA levels over an 8 day period, nor did it alter the expression of cyclophilin mRNA over 1–8 days. 5 These results suggest that chronic GABA exposure of rat cerebellar granule cells has a bi‐phasic effect on GABA A receptor subunit expression that is independent of changes to mRNA levels. Therefore, the regulation of the GABA A receptor expression by chronic agonist treatment appears to involve post‐transcriptional and/or post‐translational processes.