A1 Refereed original research article in a scientific journal
AMPA/kainate receptor-mediated up-regulation of GABA(A) receptor delta subunit mRNA expression in cultured rat cerebellar granule cells is dependent on NMDA receptor activation
Authors: Salonen V, Kallinen S, Lopez-Picon FR, Korpi ER, Holopainen IE, Uusi-Oukari M
Publisher: ELSEVIER SCIENCE BV
Publication year: 2006
Journal: Brain Research
Journal name in source: BRAIN RESEARCH
Journal acronym: BRAIN RES
Volume: 1087
First page : 33
Last page: 40
Number of pages: 8
ISSN: 0006-8993
DOI: https://doi.org/10.1016/j.brainres.2006.02.104
Abstract
We have studied the effects of AMPA/kainate receptor agonists on GABA(A) receptor subunit mRNA expression in vitro in cultured rat cerebellar granule cells (CGCs). Kainate (KA) (100 mu M) and high K+ (25 mM) dramatically up-regulated 8 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 alpha 1, alpha 6, beta 2, beta 3 or gamma 2. Up-regulation of delta 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 6 mRNA upregulation 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 CPW399-induced delta up-regulation suggesting that KA and CPW-399 treatments may induce glutamate release resulting in NMDA receptor activation, and subsequently to 6 mRNA upregulation. In CGCs, delta subunit is a component of extrasynaptic alpha 6 beta delta receptors that mediate tonic inhibition. Up-regulation of 6 during prolonged glutamate receptor activation or cell membrane depolarization may be a mechanism to increase tonic inhibition to counteract excessive excitation. (c) 2006 Elsevier B.V. All rights reserved.
We have studied the effects of AMPA/kainate receptor agonists on GABA(A) receptor subunit mRNA expression in vitro in cultured rat cerebellar granule cells (CGCs). Kainate (KA) (100 mu M) and high K+ (25 mM) dramatically up-regulated 8 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 alpha 1, alpha 6, beta 2, beta 3 or gamma 2. Up-regulation of delta 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 6 mRNA upregulation 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 CPW399-induced delta up-regulation suggesting that KA and CPW-399 treatments may induce glutamate release resulting in NMDA receptor activation, and subsequently to 6 mRNA upregulation. In CGCs, delta subunit is a component of extrasynaptic alpha 6 beta delta receptors that mediate tonic inhibition. Up-regulation of 6 during prolonged glutamate receptor activation or cell membrane depolarization may be a mechanism to increase tonic inhibition to counteract excessive excitation. (c) 2006 Elsevier B.V. All rights reserved.
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