Kinetic changes and modulation by carbamazepine on voltage-gated sodium channels in rat CA1 neurons after epilepsy.
OBJECTIVE
To study whether the functional properties of sodium channels, and subsequently the channel modulation by carbamazepine (CBZ) in hippocampal CA1 neurons can be changed after epileptic seizures.


METHODS
We used the acutely dissociated hippocampal CA1 pyramidal cells from epilepsy model rats 3 weeks and 3 months respectively after kainate injection, and whole-cell voltage-clamp techniques.


RESULTS
After long-term epileptic seizures, both sodium channel voltage-dependence of activation and steady-state inactivation shifted to more hyperpolarizing potentials, which resulted in the enlarged window current; the membrane density of sodium current decreased and the time constant of recovery from inactivation increased. CBZ displayed unchanged efficacy on sodium channels, with a similar binding rate to them, except that at higher concentrations, the voltage shift of inactivation was reduced. For the short-term kainate model rats, no differences were detected between the control and epilepsy groups.


CONCLUSIONS
These results indicate that the properties of sodium channels in acutely dissociated hippocampal neurons could be changed following long-term epilepsy, but the alternation might not be enough to induce the channel resistance to CBZ.
Sun
Guang-chun
GC
Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 320, 1098SM, the Netherlands. sungc@gmc.edu.cn
Werkman
Taco R
TR
Wadman
Wytse J
WJ
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology*; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D007608:Kainic Acid; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism* / Q000502:physiology
D000927:Anticonvulsants; D015222:Sodium Channels; D002220:Carbamazepine; D007608:Kainic Acid