'Neonatal' Nav1.2 reduces neuronal excitability and affects seizure susceptibility and behaviour

EV Gazina; BTW Leaw; KL Richards; VC Wimmer; TH Kim; TD Aumann; TJ Featherby; L Churilov; VE Hammond; CA Reid; S Petrou

Journal article

'Neonatal' Nav1.2 reduces neuronal excitability and affects seizure susceptibility and behaviour

EV Gazina, BTW Leaw, KL Richards, VC Wimmer, TH Kim, TD Aumann, TJ Featherby, L Churilov, VE Hammond, CA Reid, S Petrou

Human Molecular Genetics | Published : 2015

DOI: 10.1093/hmg/ddu562

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 NaV1.2adult mice expressing only the 'adult' NaV1.2, and compared the firing properties of pyramidal cortical neurons, as well as seizure susceptibility, between the NaV1.2adult and wild-type (WT) mice a..

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University of Melbourne Researchers

Verena Wimmer Author

Leonid Churilov Author

Christopher Reid Author

Related Projects (1)

Brain sodium channel: functional role of developmentally regulated alternative splicing

This project will identify the roles of neonatal and adult forms of a sodium channel in the function of neurons in the developing brain. Sod..

Grants

Awarded by Australian Research Council

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.