Activity of SKa-31 against seizure-like events in rat organotypic hippocampal slice cultures

Muhammad Liaquat Raza, Ismini Papageorgiou, Uwe Heinemann
Institute of Neurophysiology, Charité - Universitätsmedizin, Berlin, Germany

sK-channel plays role in regulating neuronal excitability, thus it might be of interest to suppress seizure in epileptic patients. Based on role of sK channel we aimed to test enhancer of sK-channel in rat organotypic hippocampal slice cultures (OHSCs) against seizure-like events (SLEs) induced by 4-amino-pyridine or Mg+2 free ACSF. Slice culture were prepared from p5-p7 rat pups (Kann et al., 2003) and incubated with maintained condition i.e. 5% CO2, 36.5°C. Cultures were fed every alternate day, whereas 7-14 days old cultures were used for electrophysiological recordings using interface setup.

SKa-31 (sK-channel enhancer) at dose of 150μM completely suppressed seizure-like events, standard anti-epileptic drugs sodium valporate (2mM) and carbamazepine (100μM) were also blocked SLEs induced by 4-AP. All drugs were unable to block status or late recurrent discharges induced by Mg-Free ACSF. Data suggest sK channel enhancer has potential to suppress acute seizures but not pharmacoresistant epileptic seizures.

References: Kann O, Schuchmann S, Buchheim K, Heinemann U (2003) Coupling of neuronal activity and mitochondrial metabolism as revealed by NAD(P)H fluorescence signals in organotypic hippocampal slice cultures of the rat. Neuroscience 119:87–100.

Keywords: hippocampus, epilepsy, sK channel