Journal article

'Neonatal' Na(v)1.2 reduces neuronal excitability and affects seizure susceptibility and behaviour

Elena V Gazina, Bryan TW Leaw, Kay L Richards, Verena C Wimmer, Tae H Kim, Timothy D Aumann, Travis J Featherby, Leonid Churilov, Vicki E Hammond, Christopher A Reid, Steven Petrou

HUMAN MOLECULAR GENETICS | OXFORD UNIV PRESS | Published : 2015

Abstract

Developmentally regulated alternative splicing produces 'neonatal' and 'adult' isoforms of four Na(+) channels in human brain, NaV1.1, NaV1.2, NaV1.3 and NaV1.6. Heterologously expressed 'neonatal' NaV1.2 channels are less excitable than 'adult' channels; however, functional importance of this difference is unknown. We hypothesized that the 'neonatal' NaV1.2 may reduce neuronal excitability and have a seizure-protective role during early brain development. To test this hypothesis, we generated NaV1.2(adult) mice expressing only the 'adult' NaV1.2, and compared the firing properties of pyramidal cortical neurons, as well as seizure susceptibility, between the NaV1.2(adult) and wild-type (WT) ..

View full abstract

Grants

Awarded by Australian Research Council


Awarded by National Health and Medical Research Council of Australia


Funding Acknowledgements

This work was supported by Australian Research Council Grant DP120102389 and by the Victorian Government through the Operational Infrastructure Scheme. S.P. was supported by a Senior Research Fellowship 1005050 from the National Health and Medical Research Council of Australia.