Mechanistic basis for LQT1 caused by S3 mutations in the KCNQ1 subunit of IKs.

ABSTRACT: Long QT interval syndrome (LQTS) type 1 (LQT1) has been reported to arise from mutations in the S3 domain of KCNQ1, but none of the seven S3 mutations in the literature have been characterized with respect to trafficking or biophysical deficiencies. Surface channel expression was studied using a proteinase K assay for KCNQ1 D202H/N, I204F/M, V205M, S209F, and V215M coexpressed with KCNE1 in mammalian cells. In each case, the majority of synthesized channel was found at the surface, but mutant I(Ks) current density at +100 mV was reduced significantly for S209F, which showed approximately 75% reduction over wild type (WT). All mutants except S209F showed positively shifted V(1/2)'s of activation and slowed channel activation compared with WT (V(1/2) = +17.7 +/- 2.4 mV and tau(activation) of

SUBMITTER: Eldstrom J 

PROVIDER: S-EPMC2860592 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature