Ion channels mediate the electrical properties of neurons and other excitable cells. Mutations in ion channel genes have been linked to several neurological disorders. For example, a rare familial form of epilepsy, generalized epilepsy with febrile seizures plus (GEFS+), is associated with mutations in voltage gated sodium channels. We examined how two such mutations (C121W, D188V) alter the functional properties of the channel through voltage-clamp studies in Xenopus oocytes and HEK cells respectively. D188V is located in the alpha subunit and C121W in the auxiliary beta1 subunit of the sodium channel. / The C121W mutation causes a 100 fold reduction in efficacy of current modulation as well as a reduction of current amplitude. This may cause increased sodium currents via a negative shift of the steady-state inactivation curve. alpha-D188V channels recover faster from the inactivated state which causes a resistance to frequency-dependent cumulative inactivation of current amplitude. This may contribute to cellular hyperexcitability resulting in ictal events in the epileptic patient.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.80321 |
| Date | January 2003 |
| Creators | Loukas, Andrew |
| Contributors | Ragsdale, David S. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Neuroscience.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002031532, proquestno: AAIMQ98690, Theses scanned by UMI/ProQuest. |
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