Ion channels: genetics and as a targets for antiepileptic drugs
- Author:
Kazuhiro Yamakawa
- Publication Type:Journal Article
- From:Neurology Asia
2013;18(s1):13-14
- CountryMalaysia
- Language:English
-
Abstract:
Dravet syndrome is caused by mutations of the SCN1A gene that encodes voltage-gated sodium channel
alpha-1 subunit. SCN1A-knock-in mouse with a disease-relevant nonsense mutation that we generated
reproduced the disease phenotypes. Both homozygous and heterozygous knock-in mice developed
epileptic seizures within the fi rst postnatal month. Our immunohistochemical studies showed that in
wild-type mice Nav1.1 is dominantly expressed in parvalbumin-positive inhibitory interneurons (PV
cells), intensely in its axons and moderately in somata, and mostly not observed in pyramidal cells
nor other types of interneurons including somatostatin-positive and calretinin-positive cells. These
results suggest that Nav1.1 is largely expressed in PV interneurons and plays critical roles in their
spike output, and that impaired function of PV cells would be the cellular basis of Dravet syndrome.
PV interneurons and Nav1.1 in those cells would be critical targets for antiepileptic drugs.
- Full text:P020150706592356738186.pdf
