FGF14 modulates resurgent sodium current in mouse cerebellar Purkinje neurons.
Journal Article (Journal Article)
Rapid firing of cerebellar Purkinje neurons is facilitated in part by a voltage-gated Na(+) (NaV) 'resurgent' current, which allows renewed Na(+) influx during membrane repolarization. Resurgent current results from unbinding of a blocking particle that competes with normal channel inactivation. The underlying molecular components contributing to resurgent current have not been fully identified. In this study, we show that the NaV channel auxiliary subunit FGF14 'b' isoform, a locus for inherited spinocerebellar ataxias, controls resurgent current and repetitive firing in Purkinje neurons. FGF14 knockdown biased NaV channels towards the inactivated state by decreasing channel availability, diminishing the 'late' NaV current, and accelerating channel inactivation rate, thereby reducing resurgent current and repetitive spiking. Critical for these effects was both the alternatively spliced FGF14b N-terminus and direct interaction between FGF14b and the NaV C-terminus. Together, these data suggest that the FGF14b N-terminus is a potent regulator of resurgent NaV current in cerebellar Purkinje neurons.
Full Text
Duke Authors
Cited Authors
- Yan, H; Pablo, JL; Wang, C; Pitt, GS
Published Date
- September 30, 2014
Published In
Volume / Issue
- 3 /
Start / End Page
- e04193 -
PubMed ID
- 25269146
Pubmed Central ID
- PMC4356139
Electronic International Standard Serial Number (EISSN)
- 2050-084X
Digital Object Identifier (DOI)
- 10.7554/eLife.04193
Language
- eng
Conference Location
- England