Adenylyl Cyclases: Expression in the Developing Rat Thalamus and Their Role in Absence Epilepsy

作者：Ehling Petra^*; Kanyshkova Tatyana; Baumann Arnd; Landgraf Peter; Meuth Sven G; Pape Hans Christian; Budde Thomas

来源：Journal of Molecular Neuroscience, 2012, 48(1): 45-52.

DOI：10.1007/s12031-012-9767-8

• Cyclic AMP
• Adenylyl cyclase
• Thalamocortical relay neuron
• Absence epilepsy

Adenylyl cyclases (ACs) synthesize the second messenger cyclic AMP (cAMP) which influences the function of multiple ion channels. Former studies point to a malfunction of cAMP-dependent ion channel regulation in thalamocortical relay neurons that contribute to the development of the absence epileptic phenotype of a rat genetic model (WAG/Rij). Here, we provide detailed information about the thalamic gene and protein expression of Ca2+/calmodulin-activated AC isoforms in rat thalamus. Data from WAG/Rij were compared to those from non-epileptic controls (August-Copenhagen Irish rats) to elucidate whether differential expression of ACs contributes to the dysregulation of thalamocortical activity. At one postnatal stage (P21), we found the gene expression of two specific Ca2+-activated AC isoforms (AC-1 and AC-3) to be significantly down-regulated in epileptic tissue, and we identified the isoform AC-1 to be the most prominent one in both strains. However, Western blot data and analysis of enzymatic AC activity revealed no differences between the two strains. While basal AC activity was low, cAMP production was boosted by application of a forskolin derivative up to sevenfold. Despite previous hints pointing to a major contribution of ACs, the presented data show that there is no apparent causality between AC activity and the occurrence of the epileptic phenotype.

• 出版日期2012-9