SCN1A splice variants exhibit divergent sensitivity to commonly used antiepileptic drugs.

ABSTRACT:

Purpose

A common genetic variant (rs3812718) in a splice donor consensus sequence within the neuronal sodium channel gene SCN1A (encoding Na(V) 1.1) modulates the proportion of transcripts incorporating either the canonical (5A) or alternative (5N) exon 5. A pharmacogenetic association has been reported whereby increased expression of exon 5N containing Na(V) 1.1 transcripts correlated with lower required doses of phenytoin in epileptics. We tested the hypothesis that SCN1A alternative splicing affects the pharmacology of Na(V) 1.1 channels.

Methods

To directly examine biophysical and pharmacologic differences between the exon 5 splice variants, we performed whole-cell patch clamp recording of tsA201 cells transiently coexpressing either Na(V) 1.1-5A or Na(V) 1.1-5N with the

SUBMITTER: Thompson CH 

PROVIDER: S-EPMC3093448 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature