Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures

Eva Ruusuvuori, Antje K. Huebner, Ilya Kirilkin, Alexey Y. Yukin, Peter Blaesse, Mohamed Helmy, Hyo Jung Kang, Malek El Muayed, J. Christopher Hennings, Juha Voipio, Nenad Šestan, Christian A. Hübner, Kai Kaila*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Brain carbonic anhydrases (CAs) are known to modulate neuronal signalling. Using a novel CA VII (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. CA VII 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 GABA A -receptor activation. P13-14 CA VII 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 CA VII is a key molecule in age-dependent neuronal pH regulation with consequent effects on generation of FS.

Original languageEnglish (US)
Pages (from-to)2275-2286
Number of pages12
JournalEMBO Journal
Volume32
Issue number16
DOIs
StatePublished - Aug 14 2013

Keywords

  • Carbonic anhydrase expression
  • Chloride accumulation
  • Human brain
  • Hyperthermia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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