Regulation of Calcium Channel α_1A 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 α_1A 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 α_1A subunits splice variants (α_1A-a and α_1A-b) in control and kainic acid (KA)-treated rats. Six hours after KA treatment, α_1A-a and α_1A-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 α_1A mRNA upregulation lasted for at least 7 days after KA treatment. Altogether, these results indicate that α_1A-a and α_1A-b mRNAs following seizure onset exhibit a complex and specific spatio-temporal pattern. The long-lasting changes in α_1A subunit mRNA contents suggests that VGCC may be involved in the mechanisms generating chronic focal hyperexcitability and/or cellular damage in temporal lobe epilepsy.