期刊
NATURE MEDICINE
卷 7, 期 3, 页码 331-337出版社
NATURE AMERICA INC
DOI: 10.1038/85480
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资金
- NINDS NIH HHS [NS35439, R01 NS035439, R01 NS038580, NS38580, R37 NS035439] Funding Source: Medline
Febrile seizures are the most common type of developmental seizures, affecting up to 5% of children. Experimental complex febrile seizures involving the immature rat hippocampus led to a persistent lowering of seizure threshold despite an upregulation of inhibition. Here we provide a mechanistic resolution to this paradox by showing that, in the hippocampus of rats that had febrile seizures, the long-lasting enhancement of the widely expressed intrinsic: membrane conductance I-h converts the potentiated synaptic inhibition to hyperexcitability in a frequency-dependent manner. The altered gain of this molecular inhibition-excitation converter reveals a new mechanism for controlling the balance of excitation-inhibition in the limbic system. In addition, here we show for the first time that h-channels are modified in a human neurological disease paradigm.
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