Pathological regulation of SK potassium channels in epilepsy models

• Applicants: Privatdozent Dr. Timo Kirschstein; Professor Dr. Rüdiger Köhling
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 290978607

In epilepsy research, so-called acquired channelopathies play a major role in the pathophysiology of epileptic discharges. In this context, so-called SK potassium channels are of particular interest, as they serve to dampen neuronal activity, are active mainly during prolonged, i.e. potentially pathological spiking and since pharmacological tools exist to upregulate their function. The central objective of this project is to elucidate the role of functional SK2 regulation in controlling network hyperexcitability and epileptogenesis. Specifically, by comparing data from normal and chronically and acutely epileptic tissue, we will address the mechanisms of transcriptional SK2 downregulation, possible changes in Calmodulin (CaM)-SK2 interactions (including alterations of CaM, and CaM-casein kinase interactions), and SK2 turnover and trafficking. We lastly explore a translational aspect, i.e. the possibility of inhibiting casein kinase 2 (CK2) and thereby interfering with SK2 function via CK2 phosphorylation of CaM, hypothesizing that this will reduce epileptogenicity.

• DFG Programme: Research Grants