Abstracts

Rationale: Small conductance calcium (Ca2 ) activated SK channels are critical regulator of neuronal excitability in hippocampus. Accordingly, these channels are thought to play a key role in controlling neuronal activity in acute models of epilepsy. In this study, we investigate the expression and function of SK channels in the pilocarpine model of mesial temporal lobe epilepsy. Methods: For this purpose, protein expression was assessed using western blotting assays and gene expression was analyzed using TaqMan-based probes and the quantitative real-time polymerase chain reaction (qPCR) comparative method delta-delta cycle threshold (DDCT) in samples extracted from control and epileptic rats. In addition, the effect of SK channel antagonist UCL1684 and agonist NS309 on CA1 evoked population spikes was studied using extracellualr recordings in hippocampal slices obtained from control and epileptic rats. Results: Our findings indicate no changes in protein and transcript expression of SK1 channels in chronic epileptic rats. In contrast, a significant down-regulation of SK2 and SK3 channels was detected in tissues obtained from chronic epileptic rats. Real-time quantitative PCR analysis of gene expression revealed that a significant reduction of transcripts for SK2 and SK3 channels occurred as early as 10 days following pilocarpine-induced status epilepticus and persisted during the chronic phase of the model. Moreover, bath application of UCL1684 (100 nM for 15 min) in control and epileptic slices induced a significant increase of the population spike amplitude and number of spikes in the hippocampal CA1 area. This effect was obliterated by co-administration of UCL1684 with SK channel agonist NS309 (1 ?M). Application of NS309 failed to modify population spikes in the CA1 area of slices taken from control and epileptic rats. Conclusions: These data indicate an abnormal expression of SK channels and a defective function in the pilocarpine model of temporal lobe epilepsy. Accordingly, drugs that enhance the function of SK channels can potentially act as antiepileptic drugs in temporal lobe epilepsy.