FGF14 modulates resurgent sodium current in mouse cerebellar Purkinje neurons

Rapid firing of cerebellar Purkinje neurons is facilitated in part by a voltage-gated Na(+) (Na(V)) ‘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 Na(V) channel auxiliary subunit FGF14 ‘b’ isoform, a locus for inherited spinocerebellar ataxias, controls resurgent current and repetitive firing in Purkinje neurons. FGF14 knockdown biased Na(V) channels towards the inactivated state by decreasing channel availability, diminishing the ‘late’ Na(V) 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 Na(V) C-terminus. Together, these data suggest that the FGF14b N-terminus is a potent regulator of resurgent Na(V) current in cerebellar Purkinje neurons. DOI: http://dx.doi.org/10.7554/eLife.04193.001