Alternative splicing modulates inactivation of type 1 voltage-gated sodium channels by toggling an amino acid in the first S3-S4 linker.

ABSTRACT: Voltage-gated sodium channels underlie the upstroke of action potentials and are fundamental to neuronal excitability. Small changes in the behavior of these channels are sufficient to change neuronal firing and trigger seizures. These channels are subject to highly conserved alternative splicing, affecting the short linker between the third transmembrane segment (S3) and the voltage sensor (S4) in their first domain. The biophysical consequences of this alternative splicing are incompletely understood. Here we focus on type 1 sodium channels (Nav1.1) that are implicated in human epilepsy. We show that the functional consequences of alternative splicing are highly sensitive to recording conditions, including the identity of the major intracellular anion and the recording temperature. In pa

SUBMITTER: Fletcher EV 

PROVIDER: S-EPMC3196094 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature