CHANGES IN THE MESSENGER-RNAS ENCODING SUBTYPE-I, SUBTYPE-II AND SUBTYPE-III SODIUM-CHANNEL ALPHA-SUBUNITS FOLLOWING KAINATE-INDUCED SEIZURES IN RAT-BRAIN

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 alpha subunit I, II and III in brains from control and kainate-treated rats using non-radioactive in situ h ybridization with subtype-specific digoxigenin-labelled cRNA probes. L abelling intensity was evaluated by a densitometric analysis of digiti zed images. Heterogeneous distribution of the three Na+ channel mRNAs was demonstrated in brain from adult control rats, which confirmed pre vious studies. Subtype II mRNAs were shown to be abundant in cerebellu m 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 thr ee subtypes were differentially distributed in neocortical layers. Sub type II mRNAs were present in all of the layers, but mRNAs for subtype s I and III were concentrated in pyramidal cells of neocortex layers I V-V. During kainate-induced seizures, we observed an increase in Na+ c hannel II and III mRNA levels in hippocampus. In dentate gyrus, subtyp e III mRNAs increased 3 h after KA administration to a maximum at 6 h. At this latter time, a lower increase in NaCh III mRNAs was also reco rded in areas CA1 and CA3. NaCh III overexpression in dentate gyrus pe rsisted for at least 24 h. In the same area, NaCh IT mRNAs were also i ncreased with a peak 3 h after KA injection and a return to control le vels by 24 h. No changes in NaCh I mRNAs were seen. The KA-induced up- regulation in NaCh mRNAs probably resulted in an increase in hippocamp al neuronal excitability.