Modulation of seizure-like events by the small conductance and ATP-sensitive potassium ion channels

Abstract

Potassium ion channels are extensively involved in the regulation of epileptic seizures. The small conductance calcium-sensitive potassium channels (SK channels) and ATP-sensitive potassium (K_ATP) channels are activated by calcium ion entry and decrease ATP levels, respectively. These channels can underlie the post-burst afterhyperpolarization and be upregulated during seizures, providing negative feedback during epileptic activity. Using the whole-cell patch-clamp method in rat brain slices, we investigated the effect of SK- and K_ATP-affecting drugs on seizure-like events (SLEs) in the 4-aminopyridine model of epileptic seizures in vitro. We demonstrate that SK and K_ATP channels contribute to sustaining the high-frequency firing of the principal neurons in the deep layers of the entorhinal cortex during injections of depolarizing current and epileptiform discharges. Neither the pharmacological blockade nor the activation of these channels was able to prevent the epileptiform activity in brain slices. However, the blockade of K_ATP channels increases the SLE duration, suggesting that these channels may contribute to the termination of SLEs. Thus, K_ATP channels can be considered a promising target for pharmacological interventions for the treatment of epilepsy.

Keywords: Entorhinal cortex; Epilepsy; Epilepsy model in vitro; K(ATP) channel; SK channel.