Differential and long-lasting alterations of high-voltage activated calcium currents in CA1 and dentate granule neurons after status epilepticus.

Abstract

The effects on high-voltage activated (HVA) calcium currents were examined in hippocampal CA1 cells and dentate gyrus (DG) granule neurons, 2 days (short-term; ST) and 2-3 months (long-term; LT) after electrically induced, limbic electrographic and behavioural seizures in rats. Whole-cell voltage-clamp recordings in dissociated CA1 neurons of LT rats showed a decrease in the sustained HVA calcium current amplitude and a faster inactivation of the current both in rats that had experienced a status epilepticus (post-SE rats) and those in which the stimulation did not lead to SE (non-SE rats). In CA1 neurons of LT-SE rats this resulted in a reduced Ca2+ entry through the HVA channels. Perforated-patch voltage-clamp recordings in dissociated DG granule neurons of LT-SE rats showed an increased sustained HVA current amplitude compared to controls and non-SE rats, leading to an increased Ca2+ entry via HVA calcium channels. Two days after SE, we observed an increased Ca2+ entry for a defined depolarization, although the change in HVA current amplitude and inactivation rate did not reach significance. We also observed a decrease in calbindin-D28k staining in DG post-SE neurons, but this change was not associated with a change in HVA current inactivation. The opposite changes in neuronal Ca2+ entry through HVA channels in CA1 vs. DG cells depended strongly on whether rats had experienced SE and later spontaneous seizure activity. These changes are likely to contribute to regionally different effects on local network excitability.