Regulation of calcium channel alpha(1A) subunit splice variant mRNAs in kainate-induced temporal lobe epilepsy

P/Q-type voltage-gated Ca2+ channels (VGCC) regulate neurotransmitter relea se in the hippocampus and molecular alterations of their alpha(1A) pore-for ming subunits are involved in various animal and human CNS diseases. We eva luated, using RT-PCR and in situ hybridization, the spatio-temporal activat ion of two alpha(1A) subunits splice variants (alpha(1A-a) and alpha(1A-b)) in control and kainic acid (KA)-treated rats. Six hours after KA treatment , alpha(1A-a) and alpha(1A-b) mRNAs increased, decreased or remained unchan ged with area specific patterns. These changes were evidenced in the hippoc ampus and the dentatus gyrus and absent in the cerebellum. The alpha(1A) mR NA upregulation lasted for at least 7 days after KA treatment. Altogether, these results indicate that alpha(1A-a) and alpha(1A-b) mRNAs following sei zure onset exhibit a complex and specific spatio-temporal pattern. The long -lasting changes in alpha(1A) subunit mRNA contents suggests that VGCC may be involved in the mechanisms generating chronic focal hyperexcitability an d/or cellular damage in temporal lobe epilepsy. (C) 1999 Academic Press.