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Changes in the mRNAs encoding subtypes I, II and III sodium channel alpha subunits following kainate-induced seizures in rat brain

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Journal of Neurocytology

Abstract

Several lines of evidence underscore a possible role of voltage-gated Na+ channels (NaCH) in epilepsy. We compared the regional distribution of mRNAs coding for Na+ channel α subunit I, II and III in brains from control and kainate-treated rats using non-radioactive in situ hybridization with subtype-specific digoxigenin-labelled cRNA probes. Labelling intensity was evaluated by a densitometric analysis of digitized images. Heterogeneous distribution of the three Na+ channel mRNAs was demonstrated in brain from adult control rats, which confirmed previous studies. Subtype II mRNAs were shown to be abundant in cerebellum and hippocampus. Subtype I mRNAs were also detected in these areas. Subtype III mRNAs were absent in cerebellar cortex, but significantly expressed in neurons of the medulla oblongata and hippocampus. The three subtypes were differentially distributed in neocortical layers. Subtype II mRNAs were present in all of the layers, but mRNAs for subtypes I and III were concentrated in pyramidal cells of neocortex layers IV–V. During kainate-induced seizures, we observed an increase in Na+ channel II and III mRNA levels in hippocampus. In dentate gyrus, subtype III mRNAs increased 3 h after K A administration to a maximum at 6 h. At this latter time, a lower increase in NaCh III mRNAs was also recorded in areas CA1 and CA3. NaCh III overexpression in dentate gyrus persisted for at least 24 h. In the same area, NaCh II mRNAs were also increased with a peak 3 h after K A injection and a return to control levels by 24 h. No changes in NaCh I mR NAs were seen. The K A-induced up-regulation in NaCh mR NAs probably resulted in an increase in hippocampal neuronal excitability.

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Authors and Affiliations

  1. Faculte de Medecine, Laboratoire de Biologie Cellulaire, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 5

    F. Bartolomei, M. Gastaldi, A. Massacrier & P. Cau

  2. Faculte de Medecine, Laboratoire de Biochimie, INSERM U 38, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 5

    R. Planells

  3. Luminy, IBDM, Marseille, France

    S. Nicolas

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  1. F. Bartolomei
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  2. M. Gastaldi
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  4. R. Planells
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  5. S. Nicolas
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  6. P. Cau
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Bartolomei, F., Gastaldi, M., Massacrier, A. et al. Changes in the mRNAs encoding subtypes I, II and III sodium channel alpha subunits following kainate-induced seizures in rat brain. J Neurocytol 26, 667–678 (1997). https://doi.org/10.1023/A:1018549928277

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