Abstract
In a mouse mutagenesis screen,weisolated 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 α3 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 α3 by transgenesis, which also rescued Na+,K+-ATPase activity. Our findings reveal the functional significance of the Na +,K+-ATPase α3 isoform in the control of epileptiform activity and seizure behavior.
Original language | English (US) |
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Pages (from-to) | 14085-14090 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 106 |
Issue number | 33 |
DOIs | |
State | Published - Aug 18 2009 |
Keywords
- Alpha3 Na,K ATPase
- BAC rescue
- Epilepsy
- Forward genetic screen
- Mouse
ASJC Scopus subject areas
- General