Low-voltage-activated calcium channel subunit expression in a genetic model of absence epilepsy in the rat

The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an inbred str ain of rats that display many of the characteristics of human absence epile psy. In these rats, reciprocal thalamocortical projections play a critical role in the generation of spike-and-wave discharges that characterize absen ce seizures. When compared to those of the non-epileptic control strain, ju venile animals of the GAERS strain reportedly possess higher-amplitude T-ty pe calcium currents in neurons of the thalamic reticular nucleus (nRt). We hypothesized that differences in calcium currents seen between GAERS and co ntrols result from differences in expression of genes for low-voltage-activ ated calcium channels. Quantitative in situ hybridization was used to compa re expression of alpha 1G, alpha 1H, alpha 1I, and alpha 1E calcium channel subunit mRNAs from adult and juvenile animals of the two strains. We found higher levels of alpha 1H mRNA expression in nRt neurons of juvenile anima ls (34.9 +/- 2.3 vs. 28.4 +/- 1.8 grains/10(3) pixels, p < 0.05), perhaps a ccounting in part for earlier reports of elevated T-type current amplitude in those cells. In adult GAERS animals, we found elevated levels of alpha 1 G mRNA in neurons of the ventral posterior thalamic relay nuclei (64.8 +/- 3.5 vs. 53.5 +/- 1.7 grains/10(3) pixels, p < 0.05), as well as higher leve ls of alpha 1H mRNA in nRt neurons (32.6 +/- 0.8 vs. 28.2 +/- 1.6 grains/10 (3) pixels, p < 0.05). These results suggest that the epileptic phenotype a pparent in adult GAERS may result in part from these significant, albeit sm all (similar to 15-25%), elevations in T-type calcium channel mRNA levels. (C) 2000 Elsevier Science B.V. All rights reserved.