Suppression of epileptiform activity by a single short-duration electric field in rat hippocampus in vitro

Abstract

The mechanisms behind the therapeutic effects of electrical stimulation of the brain in epilepsy and other disorders are poorly understood. Previous studies in vitro have shown that uniform electric fields can suppress epileptiform activity through a direct polarizing effect on neuronal membranes. Such an effect depends on continuous DC stimulation with unbalanced charge. Here we describe a suppressive effect of a brief (10 ms) DC field on stimulus-evoked epileptiform activity in rat hippocampal brain slices exposed to Cs(+) (3.5 mM). This effect was independent of field polarity, was uncorrelated to changes in synchronized population activity, and persisted during blockade of synaptic transmission with Cd(2+) (500 μM). Antagonists of A(1), P(2X), or P(2Y) receptors were without effect. The suppressive effect depended on the alignment of the external field with the somato-dendritic axis of CA1 pyramidal cells; however, temporal coincidence with the epileptiform activity was not essential, as suppression was detectable for up to 1 s after the field. Pyramidal cells, recorded during epileptiform activity, showed decreased discharge duration and truncation of depolarizing plateau potentials in response to field application. In the absence of hyperactivity, the applied field was followed by slow membrane potential changes, accompanied by decreased input resistance and attenuation of the depolarizing afterpotential following action potentials. These effects recovered over a 1-s period. The study suggests that a brief electric field induces a prolonged suppression of epileptiform activity, which can be related to changes in neuronal membrane properties, including attenuation of signals depending on the persisting Na(+) current.