In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 33 ( 2009-08-18), p. 14085-14090
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 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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0904817106
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2009
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
