XE991 Reverses Enhanced Short-Term Plasticity in Rat Epileptic CA1.

Background/Objectives: Recent evidence has suggested a transcriptional reduction in Kv7 potassium channels in the CA1 area of acquired experimental epilepsy, but presynaptic Kv7 channels might be spared. Here, we tested the influence of the Kv7 channel blocker XE991 on two forms of short-term plasticity, which are supposed to be presynaptic in nature: post-tetanic potentiation and paired-pulse ratio. Methods: Systemic pilocarpine was administered to induce status epilepticus and chronic epilepsy in the rat. In the chronically epileptic CA1 area, extracellular electrophysiological experiments were performed to analyze paired-pulse ratio before and after tetanic stimulation (100 Hz, 1 s). Results: Both the post-tetanic potentiation and the paired-pulse ratio were significantly higher in the epileptic CA1 as compared to control tissue (Cohen's d > 3; n = 10-11 slices from 3-4 animals per group). While pharmacological inhibition of Kv7 channels with XE991 had no effect on these measures in control CA1, it significantly reversed both forms of enhanced short-term plasticity in the epileptic CA1 to control levels (Cohen's d > 3; n = 10-11 slices from 3 animals per group). Conclusions: The epileptic CA1 showed enhanced short-term plasticity, which was not due to the loss of Kv7 channels in the epileptic CA1 subfield, since it was reversed by XE991. Therefore, our findings provide indirect evidence that the presynaptic Kv7 channel function may be at least partially intact in the epileptic CA1. It may be speculated whether potassium channel activators could pose a risk to enhance rather than depress short-term plasticity at Schaffer collateral-CA1 synapses in epilepsy.