0 avis
Q/R editing of the rat GluR5 and GluR6 kainate receptors in vivo and in vitro: evidence for independent developmental, pathological and cellular regulation.
Archive ouverte
International audience. Kainate (KA) is a potent neuroexcitatory agent in several areas of the adult brain, with convulsant and excitotoxic properties that increase as ontogeny proceeds. Besides its depolarizing actions, KA may enhance intracellular accumulation of Ca2+ to promote selective neuronal damage. The effects of KA are mediated by specific receptors recently considered to be involved in fast neurotransmission and that can be activated synaptically. KA receptors, e.g. GluR5 and GluR6 have been characterized by molecular cloning. Structure-function relationships indicate that in the MII domain of these KA receptors, a glutamine (Q) or arginine (R) residue determines ion selectivity. The arginine stems from post-transcriptional editing of the GluR5 and GluR6 pre-RNAs, and the unedited and edited versions of GluR6 elicit distinct Ca2+ permeability. Using a PCR-based approach, we show that in vivo, Q/R editing in the GluR5 and GluR6 mRNAs is modulated during ontogeny and differs substantially in a variety of nervous tissues. GluR5 editing is highest in peripheral nervous tissue, e.g. the dorsal root ganglia, where GluR6 expression is barely detectable. In contrast, GluR6 editing is maximal in forebrain and cerebellar structures where GluR5 editing is lower. Intra-amygdaloid injections of KA provide a model of temporal lobe epilepsy, and we show that following seizures, the extent of GluR5 and GluR6 editing is altered in the hippocampus. However, in vitro, high levels of glutamate and potassium-induced depolarizations have no effect on GluR5 and GluR6 Q/R editing. GluR6 editing is rapidly enhanced to maximal levels in primary cultures of cerebellar granule neurons but not in cultured hippocampal pyramidal neurons. Finally, we show that cultured glial cells express partially edited GluR6 mRNAs. Our results indicate that Q/R editing of GluR5 and GluR6 mRNAs is structure-, cell type- and time-dependent, and suggest that editing of these mRNAs is not co-regulated.
Consulter en ligne
Suggestions
Du même auteur
