Regulation of Calcium Channel α1A Subunit Splice Variant mRNAs in Kainate-Induced Temporal Lobe Epilepsy

Abstract

P/Q-type voltage-gated Ca2+ channels (VGCC) regulate neurotransmitter release in the hippocampus and molecular alterations of their α1A pore-forming subunits are involved in various animal and human CNS diseases. We evaluated, using RT-PCR and in situ hybridization, the spatio-temporal activation of two α1A subunits splice variants (α1A-a and α1A-b) in control and kainic acid (KA)-treated rats. Six hours after KA treatment, α1A-a and α1A-b mRNAs increased, decreased or remained unchanged with area specific patterns. These changes were evidenced in the hippocampus and the dentatus gyrus and absent in the cerebellum. The α1A mRNA upregulation lasted for at least 7 days after KA treatment. Altogether, these results indicate that α1A-a and α1A-b mRNAs following seizure onset exhibit a complex and specific spatio-temporal pattern. The long-lasting changes in α1A subunit mRNA contents suggests that VGCC may be involved in the mechanisms generating chronic focal hyperexcitability and/or cellular damage in temporal lobe epilepsy.