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Molecular and functional changes in voltage-dependent na+ channels following pilocarpine-induced status epilepticus in rat dentate granule cells
| Content Provider | Semantic Scholar |
|---|---|
| Author | Ellerkmann, Richard Klaus Remy, Sebastian Chen, Jian Jhen Sochivko, Dmitry Beck, Heinz |
| Copyright Year | 2003 |
| Abstract | Status epilepticus (S.E.) is known to lead to a large number of changes in the expression of voltage-dependent ion channels and neurotransmitter receptors. In the present study, we examined whether an episode of S.E. induced by pilocarpine in vivo alters functional properties and expression of voltage-gated Na(+) channels in dentate granule cells (DGCs) of the rat hippocampus. Using patch-clamp recordings in isolated DGCs, we show that the voltage-dependent inactivation curve is significantly shifted toward depolarizing potentials following S.E. (half-maximal inactivation at -43.2+/-0.6 mV) when compared with control rats (-48.2+/-0.8 mV, P<0.0001). The voltage-dependent activation curve is significantly shifted to more negative potentials following S.E., with half-maximal activation at -28.6+/-0.8 mV compared with -25.8+/-0.9 mV in control animals (P<0.05). The changes in voltage dependence resulted in an augmented window current due to increased overlap between the activation and inactivation curve. In contrast to Na(+) channel voltage-dependence, S.E. caused no changes in the kinetics of fast or slow recovery from inactivation. The functional changes were accompanied by altered expression of Na(+) channel subunits measured by real-time reverse transcription-polymerase chain reaction in dentate gyrus microslices. We investigated expression of the pore-forming alpha subunits Na(v)1.1-Na(v)1.3 and Na(v)1.5-Na(v)1.6, in addition to the accessory subunits beta(1) and beta(2). The Na(v)1.2 and Na(v)1.6 subunit as well as the beta(1) subunit were persistently down-regulated up to 30 days following S.E. The beta(2) subunit was transiently down-regulated on the first and third day following S.E. These results indicate that differential changes in Na(+) channel subunit expression occur in concert with functional changes. Because coexpression of beta subunits is known to robustly shift the voltage dependence of inactivation in a hyperpolarizing direction, we speculate that a down-regulation of beta-subunit expression may contribute to the depolarizing shift in the inactivation curve following S.E. |
| Starting Page | 323 |
| Ending Page | 333 |
| Page Count | 11 |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/S0306-4522(03)00168-4 |
| PubMed reference number | 12770549 |
| Journal | Medline |
| Volume Number | 119 |
| Alternate Webpage(s) | http://www.meb.uni-bonn.de/agBeck/cms/upload/PDF/Neuroscience_Sodium_channels.pdf |
| Alternate Webpage(s) | http://www.meb.uni-bonn.de/agBeck/cms/upload/homepage/beck/pdf/Neuroscience_Sodium_channels.pdf |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S0306452203001684 |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S0306452203001684?dgcid=api_sd_search-api-endpoint |
| Alternate Webpage(s) | https://doi.org/10.1016/S0306-4522%2803%2900168-4 |
| Journal | Neuroscience |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
