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

• Published in: Brain research Vol. 1087; no. 1; pp. 33 - 40
• Main Authors: SALONEN, Virpi, KALLINEN, Sampsa, LOPEZ-PICON, Francisco R, KORPI, Esa R, HOLOPAINEN, Irma E, UUSI-OUKARI, Mikko
• Format: Journal Article
• Language: English
• Published: London Elsevier 04.05.2006; Amsterdam; New York, NY
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Cell Survival - drug effects; Cells, Cultured; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cerebellum - cytology; Dose-Response Relationship, Drug; Drug Interactions; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Neurons - drug effects; Neurons - physiology; Potassium - pharmacology; Protein Subunits - genetics; Protein Subunits - metabolism; Rats; Rats, Sprague-Dawley; Receptors, GABA-A - genetics; Receptors, GABA-A - metabolism; Receptors, Glutamate - classification; Receptors, Glutamate - physiology; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; Tetrazolium Salts; Thiazoles; Up-Regulation - drug effects; Up-Regulation - physiology; Vertebrates: nervous system and sense organs; Cerebellum; Kainate; Granule neuron; Rat; Rodentia; Central nervous system; Activation; Glutamate receptor; Gene expression; Subunit; Encephalon; Kainate receptor; Vertebrata; AMPA receptor; Mammalia; Animal; Cerebellar granule cell; NMDA receptor; GABAA receptor; Gabaergic receptor A
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.02.104

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 microM) and high K(+) (25 mM) dramatically up-regulated delta 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 GABA(A) receptor subunits alpha1, alpha6, beta2, beta3 or gamma2. 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 delta 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 delta up-regulation suggesting that KA and CPW-399 treatments may induce glutamate release resulting in NMDA receptor activation, and subsequently to delta mRNA up-regulation. In CGCs, delta subunit is a component of extrasynaptic alpha6betadelta receptors that mediate tonic inhibition. Up-regulation of delta during prolonged glutamate receptor activation or cell membrane depolarization may be a mechanism to increase tonic inhibition to counteract excessive excitation.