論文 - 詳細
| RRC ID | 21528 |
|---|---|
| 著者 | Clapcote SJ, Duffy S, Xie G, Kirshenbaum G, Bechard AR, Rodacker Schack V, Petersen J, Sinai L, Saab BJ, Lerch JP, Minassian BA, Ackerley CA, Sled JG, Cortez MA, Henderson JT, Vilsen B, Roder JC. |
| タイトル | Mutation I810N in the alpha3 isoform of Na+,K+-ATPase causes impairments in the sodium pump and hyperexcitability in the CNS. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
In a mouse mutagenesis screen, we isolated a mutant, Myshkin (Myk), with autosomal dominant complex partial and secondarily generalized seizures, a greatly reduced threshold for hippocampal seizures in vitro, posttetanic hyperexcitability of the CA3-CA1 hippocampal pathway, and neuronal degeneration in the hippocampus. Positional cloning and functional analysis revealed that Myk/+ mice carry a mutation (I810N) which renders the normally expressed Na(+),K(+)-ATPase alpha3 isoform inactive. Total Na(+),K(+)-ATPase activity was reduced by 42% in Myk/+ brain. The epilepsy in Myk/+ mice and in vitro hyperexcitability could be prevented by delivery of additional copies of wild-type Na(+),K(+)-ATPase alpha3 by transgenesis, which also rescued Na(+),K(+)-ATPase activity. Our findings reveal the functional significance of the Na(+),K(+)-ATPase alpha3 isoform in the control of epileptiform activity and seizure behavior. |
| 巻・号 | 106(33) |
| ページ | 14085-90 |
| 公開日 | 2009-8-18 |
| DOI | 10.1073/pnas.0904817106 |
| PII | 0904817106 |
| PMID | 19666602 |
| PMC | PMC2729024 |
| MeSH | Animals Base Sequence COS Cells Central Nervous System / metabolism* Chlorocebus aethiops Hippocampus / metabolism Male Mice Mice, Inbred C57BL Molecular Sequence Data Mutation* Seizures / genetics Seizures / pathology Sequence Homology, Nucleic Acid Sodium-Potassium-Exchanging ATPase / genetics Sodium-Potassium-Exchanging ATPase / metabolism* |
| IF | 9.412 |
| 引用数 | 95 |
| WOS 分野 | NEUROSCIENCES |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 15 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| 遺伝子材料 | MSM Mouse BAC (RDB04214) MSMg01–344N17 |