Investigating genetic forms of epilepsy allows for improved understanding of epilepsy pathophysiology in general. Mutations in voltage-gated sodium channels are a frequent cause of genetic forms of epilepsy. First we constructed a computational model of one sodium channel isoform and an epilepsy-associated mutation that refined our knowledge of how sodium channels inactivate. We next utilized a heterologous expression system to biophysically and biochemically characterize epilepsy-associated mutations. We found that aberrant cell surface expression as well as biophysical abnormalities may underlie some epilepsy syndromes. Finally we performed experiments in a transgenic mouse model system of epilepsy to examine the effect of genetic modifiers on sodium channel function. In summary, this research utilized three different model systems to improve our understanding of genetic forms of epilepsy.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-06302008-153406 |
| Date | 17 July 2008 |
| Creators | Misra, Sunita N |
| Contributors | Robert L. Macdonald, Vsevolod V. Gurevich, Alfred L. George, Jr., P. Jeffrey Conn, Danny G. Winder, Gregory Mathews |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-06302008-153406/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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