Sodium channels and epilepsy electrophysiology

Abstract

We examined the electrophysiology of epilepsy in the simplest system that exhibits epileptiform activity: microisland cultures that contain only one neuron. Some of these solitary excitatory hippocampal neurons generate the 'ictal' epileptiform activity characteristic of seizures. These neurons have endogenous (non-transmitter-mediated) bursts of activity that last for many seconds and appear to be driven by a persistent Na+ current. We examined this persistent Na+ current at the single channel level by recording the late openings of Na+ channels using outside-out patch recordings. Phenytoin reduced the probability of these late channel openings, but had less effect on the early channel openings that make up the peak Na+ current. The reduction of late channel openings was larger with pulses to more depolarized voltages. In contrast, the effect on early channel openings was similar at all voltages. There was little effect of phenytoin on the duration of channel openings and no effect on open channel current. This suggests that the persistent Na+ current is crucial in generating seizures. A good strategy for selecting anticonvulsants may be to search for drugs that more selectively block the persistent Na+ current at depolarized voltages. Such drugs could combine effectiveness and reduced side effects.