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Acta Pharmacologica Sinica 2006 December; 27 (12): 1537-1546; doi: 10.1111/j.1745-7254.2006.00452.x |
| Original Article | [ Full text ] |
| Kinetic changes and modulation by carbamazepine on voltage-gated sodium channels in rat CA1 neurons after epilepsy |
Guang-chun SUN2,3,4, Taco R WERKMAN3, Wytse J WADMAN3 2Department of Pharmacology, Guiyang Medical College, Guiyang 550004, China; 3Swammerdam Institute for Life Sciences, University of
Amsterdam, Kruislaan 3201098, the Netherlands |
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Aim: 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.
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Keywords: sodium channel; voltage clamp; kainate model; epilepsy; hippocampus; carbamazepine |
| 1 Project supported by National Epilepsy Funds of the Netherlands (No 98-17). |
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