The slow Ca2+-dependent K+-current facilitates synchronization of hyperexcitable pyramidal neurons

Studies on in vivo and in vitro epilepsy models have shown that progression and maintenance of epileptiform activity can be affected by the slow Ca2+-dependent K+ current (IsAHP). This study aimed to investigate the influence of the IsAHP on population activity and single cell activity during the transition from the interictal- to the ictal-like phase of an epileptiform field potential induced by Cs+. Extracellular and intracellular recordings were performed in area CA1 on 400 μm thick hippocampal slices from adult male Wistar rats. During maintained exposure to Cs+, the transition between the two phases underwent a slow, time-dependent change, where synchronized population activity gradually disappeared and a plateau-like prolongation of the interictal-like phase emerged. In parallel, the size of the ictal-like phase increased. These effects could be ascribed to a gradual block of the IsAHP and were mimicked by the IsAHP antagonists carbacholine (2 μM), isoproterenol (4 μM) and Ba2+ (0.2 mM). Cessation of population activity generally occurred without a concomitant decrease in firing rate of single CA1 pyramidal neurons, but was accompanied by the disappearance of hyperpolarizing prepotentials, indicating a shift in the mechanism of action potential initiation. These findings suggest that the presence of the IsAHP increases the tendency of hyperexcitable neurons to fire in synchrony, but at the same time serves to dampen the ictal-like activity that follows the hyperexcitable state. Our data indicate that both effects can be attributed to the influence of this current on the steady-state membrane potential in the period of the transition from interictal- to ictal-like activity.