Potassium-induced enhancement of persistent inward current in hippocampal neurons in isolation and in tissue slices

Abstract

Previous work suggested a role for the voltage-dependent persistent sodium current, I Na,P, in the generation of seizures and spreading depression (SD). Ordinarily, I Na,P is small in hippocampal neurons. We investigated the effect of raising external K + concentration, [K +] o, on whole-cell persistent inward current in freshly isolated hippocampal CA1 pyramidal neurons. I Na,P was identified by TTX-sensitivity and dependence on external Na + concentration. When none of the ion channels were blocked, I Na,P was not usually detectable, probably because competing K + current masked it, but after raising [K +] o I Na,P appeared, while K + currents diminished. With K + channels blocked, I Na,P could usually be evoked in control solution and raising [K +] o caused its reversible increase in most cells. The increase did not depend on external calcium [Ca 2+] o. In CA1 pyramidal neurons in hippocampal slices a TTX-sensitive persistent inward current was always recorded and when [K +] o was raised, it was reversibly enhanced. Strong depolarization evoked irregular current fluctuations, which were also augmented in high [K +] o. The findings support a role of potassium-mediated positive feedback in the generation of seizures and spreading depression.