Sodium currents in isolated rat CA1 pyramidal and dentate granule neurones in the post-status epilepticus model of epilepsy.
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.
Ketelaars
S O
SO
Swammerdam Institute for Life Sciences, Section Neurobiology, University of Amsterdam, Kruislaan 320, 1098 SM, Amsterdam, The Netherlands. ketelaars@sciences.uva.nl
Gorter
J A
JA
van Vliet
E A
EA
Lopes da Silva
F H
FH
Wadman
W J
WJ
D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*; D013226:Status Epilepticus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D015222:Sodium Channels