期刊
EMBO JOURNAL
卷 32, 期 16, 页码 2275-2286出版社
WILEY
DOI: 10.1038/emboj.2013.160
关键词
carbonic anhydrase expression; chloride accumulation; GABA(A) receptor; human brain; hyperthermia
资金
- Academy of Finland
- Sigrid Juselius Foundation
- Jane and Aatos Erkko Foundation
- DFG
- NIMH [MH081896]
Brain carbonic anhydrases (CAs) are known to modulate neuronal signalling. Using a novel CAVII (Car7) knockout (KO) mouse as well as a CA II (Car2) KO and a CA II/VII double KO, we show that mature hippocampal pyramidal neurons are endowed with two cytosolic isoforms. CAVII is predominantly expressed by neurons starting around postnatal day 10 (P10). The ubiquitous isoform II is expressed in neurons at P20. Both isoforms enhance bicarbonate-driven GABAergic excitation during intense GABAA-receptor activation. P13-14 CAVII KO mice show behavioural manifestations atypical of experimental febrile seizures (eFS) and a complete absence of electrographic seizures. A low dose of diazepam promotes eFS in P13-P14 rat pups, whereas seizures are blocked at higher concentrations that suppress breathing. Thus, the respiratory alkalosis-dependent eFS are exacerbated by GABAergic excitation. We found that CA VII mRNA is expressed in the human cerebral cortex before the age when febrile seizures (FS) occur in children. Our data indicate that CAVII is a key molecule in age-dependent neuronal pH regulation with consequent effects on generation of FS.
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