Editing status at the Q/R site of the GluR2 and GluR6 glutamate receptor subunits in the surgically excised hippocampus of patients with refractory epilepsy.
The editing status of mRNA at the Q/R site of the glutamate receptor subunits GluR2 and GluR6 modulates channel conductivity and ion selectivity of ionotropic AMPA/KA receptors. Alteration of the editing process may be involved in the debilitating effects of epilepsy. The ratio of unedited/edited (Q/R) forms of GluR2 and GluR6 subunits was examined in conjunction with the expression of two double-stranded RNA-specific adenosine deaminases (DRADA) in surgically excised hippocampus from patients with refractory epilepsy compared with that of control samples. In the majority of patients with long histories of epilepsy, the GluR2 transcript was detected in the completely edited form, however, in two (out of 16 tested) hippocampal samples of young subjects (2 and 10 years old) we were able to identify the unedited transcript of GluR2 subunit. The proportion of unedited fraction of GluR6(Q) subunit was decreased to 9% compared to control human hippocampus. We conclude that the editing process in epileptic specimens is selectively affected by seizure activity in the epileptic focus.
Department of Physiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
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Grigorenko
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Bell
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Glazier
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Pons
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Deadwyler
D000243:Adenosine Deaminase / Q000378:metabolism; D000328:Adult; D002648:Child; D004591:Electrophoresis, Polyacrylamide Gel; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017393:RNA Editing / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism*; D015183:Restriction Mapping; D000097806:GluK2 Kainate Receptor
D000243:Adenosine Deaminase; D012333:RNA, Messenger; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor; C104722:glutamate receptor ionotropic, AMPA 2