Effect of Gap-Junctıon Inhıbıtıon on High-Frequency Oscillations Under Hyperexcitability: An In Vitro Electrophysiological Study

Objective: High Frequency Oscillations (HFO), covers the frequency band between 80-500 Hz component of the electrical activity of brain, is considered a marker for epileptic seizures. We investigated the contribution of gap-junction to HFOs in cortex. Methods: HFOs were investigated in two different frequency bands: 80-200 Hz accepted as ripple and 250-500 HZ as fast ripples. HFO’s detected from electrophysiological recordings of 4AP-induced seizures in fresh brain slices. Then, gap-junction blockers were applied and their effects on power of HFOs were followed. Effects of Flufanemic acid (100 μM, n=10), a connexin blocker, Probenecid (200 μM, n=8), a pannexin-1 blocker, were analyzed. Power spectrum analyses of the relevant frequency ranges were performed. The effects of the blockers on 0-40 Hz frequency also analyzed. Results: Flufenamic acid significantly reduced 0-40 Hz frequency band and ripple discharges, and had no effect on fast ripples. Probenecid application reduced the 0-40 Hz, ripple and fast ripple frequency range, but did not change significantly. Conclusion: This is the first study in which two gap junction blockers, flufenamic acid and probenecid, were applied under the same experimental conditions and their effectiveness was compared with each other. HFO has been the subject of many studies in recent years. The detection of these oscillations and their onset regions provide deep information about the seizure that will develop. Future studies will shed light on unanswered questions in epilepsy disease and contribute to the development of seizure pathogenesis and new treatment methods.