Conservation of alternative splicing in sodium channels reveals evolutionary focus on release from inactivation and structural insights into gating.

ABSTRACT:

Key points

Sodium channels are critical for supporting fast action potentials in neurons; even mutations which cause small changes in sodium channel activity can have devastating consequences for the function of the nervous system. Alternative splicing also changes the activity of sodium channels, and while it is highly conserved, it is not known whether the functional role of this splicing is also conserved. Our data reveal that splicing has a highly conserved impact on the availability of sodium channels during trains of rapid stimulations, and suggest that in one mammalian channel, Nav1.1 encoded by SCN1A, the increased availability of one splice variant is detrimental. A model reproducing the effects of splicing on channel behaviour suggests that the voltage sensor in the first

SUBMITTER: Liavas A 

PROVIDER: S-EPMC5811987 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature