Elsevier

Neuroscience

Volume 105, Issue 1, 16 July 2001, Pages 109-120
Neuroscience

Sodium currents in isolated rat CA1 pyramidal and dentate granule neurones in the post-status epilepticus model of epilepsy

https://doi.org/10.1016/S0306-4522(01)00176-2Get rights and content

Abstract

Status epilepticus (SE) was induced in the rat by long-lasting electrical stimulation of the hippocampus. After a latent period of 1 week, spontaneous seizures occurred which increased in frequency and severity in the following weeks, finally culminating after 3 months in a chronic epileptic state. In these animals we determined the properties of voltage-dependent sodium currents in acutely isolated CA1 pyramidal neurones and dentate granule cells using the whole-cell voltage-clamp technique.

The conductance of the fast transient sodium current was larger in SE rats (84±7 nS versus 56±6 nS) but related to a difference in cell size so that the neurones had a similar specific sodium conductance (control: 7.8±0.8 nS/pF, SE: 6.7±0.8 nS/pF). Current activation and inactivation were characterised by a Boltzmann function. After SE the voltage dependence of activation was shifted to more negative potentials (control: −45.1±1.4 mV, SE: −51.5±2.9 mV, P<0.05). In combination with a small shift in the voltage dependence of inactivation to more depolarised potentials (control: −68.8±2.3 mV, SE: −66.3±2.3 mV), it resulted in a window current that was much increased in the SE neurones (median: 64 pA in control, 217 pA in SE, P<0.05). The peak of this window current shifted to more hyperpolarised potentials (control: −44 mV, SE: −50 mV, P<0.05). No differences were found in the sodium currents analysed in dentate granule cells of control and SE animals.

The changes observed in CA1 neurones after SE contribute to enhanced excitability in particular when membrane potential is near firing threshold. They can, at least partly, explain the lower threshold for epileptic activity in SE animals. The comparison of CA1 with DG neurones in the same rats demonstrates a differential response in the two cell types that participated in very similar seizure activity.

Section snippets

Animals and electrode implantation

Eleven adult male Sprague–Dawley rats (Harlan, Zeist, The Netherlands), weighing 385 g at the time of decapitation, were used in this study. The rats were housed in individual cages under a controlled environment (21±1°C; humidity 60%; lights on 08.00–20.00 h). Food and water were available ad libitum. Rats were anaesthetised with an intra-muscular injection of ketamine/xylazine (57/9 mg/kg) and placed in a stereotactic apparatus. For stimulation of the angular bundle, insulated stainless steel

Epileptic state

Long-lasting repetitive stimulation evoked in most rats SE that lasted for 1 h or longer. Rats that did not show SE after stimulation were not incorporated in this study. After stimulation the animals were monitored for up to 3 months. From the second week onward, spontaneous seizures of increasing intensity and severity were recorded. The five chronic epileptic animals incorporated in this study experienced between 4–40 seizures per day of quite variable intensity and duration. All rats had

Discussion

In this study we investigated sodium currents in neurones isolated from the hippocampal CA1 and DG areas of rats that displayed spontaneous seizures 3 months after an electrically induced SE. In the chronic epileptic phase, the sodium conductance per cell was significantly reduced in the CA1 neurones from the SE group, but when expressed as specific sodium conductance this difference vanished, due to a smaller cell size. The kinetics of current activation, inactivation and recovery from

Conclusions

The most prominent difference observed after SE in CA1 was a large window current that had about three times the peak amplitude of controls and was shifted 6 mV to more hyperpolarised potentials. The difference in sodium current could cause spontaneous seizures. It is not clear whether the epileptic activity also directly or indirectly affects the sodium current, thereby creating a feedback loop that maintains the epileptic state. Our observations do not exclude other factors like neurogenesis,

Acknowledgements

These investigations were supported by the National Epilepsy Fund-‘The Power of the Small’, Project Number 98-17.

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