title: Adenylyl cyclases: expression in the developing rat thalamus and their role in absence epilepsy.
abstract: 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 Ca(2+)/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 Ca(2+)-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.
authors.affiliation: Neurology Clinic-Inflammatory Disorders of the Nervous System and Neurooncology, and Institute of Physiology I - Neuropathophysiology, Westfälische Wilhelms-University, ICB, Mendelstr. 7, 48149, Muenster, Germany. Petra.Ehling@uni-muenster.de
authors.forename: Petra
authors.initials: P
authors.lastname: Ehling
authors.forename: Tatyana
authors.initials: T
authors.lastname: Kanyshkova
authors.forename: Arnd
authors.initials: A
authors.lastname: Baumann
authors.forename: Peter
authors.initials: P
authors.lastname: Landgraf
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
authors.forename: Thomas
authors.initials: T
authors.lastname: Budde
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000201:enzymology; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D013788:Thalamus / Q000166:cytology / Q000201:enzymology* / Q000502:physiology*
chemical_list: D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C421784:adenylate cyclase 3; C106670:adenylyl cyclase 1; C118292:adenylyl cyclase 8