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AMPA/kainate receptor-mediated up-regulation of GABAA receptor δ subunit mRNA expression in cultured rat cerebellar granule cells is dependent on NMDA receptor activation
- Source :
-
Brain Research . May2006, Vol. 1087 Issue 1, p33-40. 8p. - Publication Year :
- 2006
-
Abstract
- Abstract: We have studied the effects of AMPA/kainate receptor agonists on GABAA receptor subunit mRNA expression in vitro in cultured rat cerebellar granule cells (CGCs). Kainate (KA) (100 μM) and high K+ (25 mM) dramatically up-regulated δ subunit mRNA expression to 500–700% of that in control cells grown in low K+ (5 mM). KA or high K+ had no effect on the expression of the other major GABAA receptor subunits α1, α6, β2, β3 or γ2. Up-regulation of δ mRNA was also detected with the AMPA receptor-selective agonist CPW-399 and to a lesser extent with the KA receptor-selective agonist ATPA. AMPA/kainate receptor-selective antagonist DNQX completely inhibited KA-, CPW-399- and ATPA-induced δ mRNA up-regulation indicating that the effects were mediated via AMPA and KA receptor activation. NMDA receptor-selective antagonist MK-801 inhibited 76% of the KA- and 57% of the CPW-399-induced δ up-regulation suggesting that KA and CPW-399 treatments may induce glutamate release resulting in NMDA receptor activation, and subsequently to δ mRNA up-regulation. In CGCs, δ subunit is a component of extrasynaptic α6βδ receptors that mediate tonic inhibition. Up-regulation of δ during prolonged glutamate receptor activation or cell membrane depolarization may be a mechanism to increase tonic inhibition to counteract excessive excitation. [Copyright &y& Elsevier]
- Subjects :
- *GABA
*MESSENGER RNA
*PROPIONIC acid
*METHYL aspartate
Subjects
Details
- Language :
- English
- ISSN :
- 00068993
- Volume :
- 1087
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Brain Research
- Publication Type :
- Academic Journal
- Accession number :
- 21050930
- Full Text :
- https://doi.org/10.1016/j.brainres.2006.02.104